1
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Duke LC, Cone AS, Sun L, Dittmer DP, Meckes DG, Tomko RJ. Tetraspanin CD9 alters cellular trafficking and endocytosis of tetraspanin CD63, affecting CD63 packaging into small extracellular vesicles. J Biol Chem 2025:108255. [PMID: 39909378 DOI: 10.1016/j.jbc.2025.108255] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2024] [Revised: 01/13/2025] [Accepted: 01/27/2025] [Indexed: 02/07/2025] Open
Abstract
Small extracellular vesicles (sEVs) are particles secreted from cells that play vital roles both in normal physiology and in human disease. sEVs are highly enriched in tetraspanin proteins, such as CD9 and CD63, and contain tetraspanin-enriched membrane microdomains involved in loading of sEVs with macromolecule cargoes and in sEV biogenesis. However, the precise roles of individual tetraspanins in sEV biogenesis and cargo loading remain poorly understood. Here, we report that CD9 negatively regulated CD63 trafficking to tetraspanin-enriched microdomains and its subsequent packaging into small EVs, whereas CD63 had no discernable effect on CD9 localization or packaging. Using super resolution microscopy of individual vesicles, we showed that CD9 governs the fraction of sEVs that are loaded with CD63. Interestingly, CD9-dependent suppression of CD63 packaging was rescued by pharmacological blockade of endocytosis. Together, our data support a model where CD9 contributes to the regulation and secretion of CD63 in an endocytosis-dependent manner to reprogram the contents of sEVs and tetraspanin-enriched microdomains.
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Affiliation(s)
- Leanne C Duke
- Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, 32306, United States of America.
| | - Allaura S Cone
- Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, United States of America
| | - Li Sun
- Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, 32306, United States of America
| | - Dirk P Dittmer
- Department of Microbiology and Immunology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, United States of America
| | | | - Robert J Tomko
- Department of Biomedical Sciences, Florida State University College of Medicine, Tallahassee, FL, 32306, United States of America
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2
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Okuyan HM, Coşkun A, Begen MA. Current status, opportunities, and challenges of exosomes in diagnosis and treatment of osteoarthritis. Life Sci 2025; 362:123365. [PMID: 39761740 DOI: 10.1016/j.lfs.2024.123365] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 11/22/2024] [Accepted: 12/31/2024] [Indexed: 01/19/2025]
Abstract
Osteoarthritis (OA) is a progressive joint disease that is a frequent reason for pain and physical dysfunction in adults, with enormous social and economic burden. Although ongoing scientific efforts in recent years have made considerable progress towards understanding of the disease's molecular mechanism, the pathogenesis of OA is still not fully known, and its clinical challenge remains. Thus, elucidating molecular events underlying the initiation and progression of OA is crucial for developing novel diagnostic and therapeutic approaches that could facilitate effective clinical management of the illness. Exosomes, extracellular vesicles containing various cellular components with approximately a diameter of 100 nm, act as essential mediators in physiological and pathological processes by modulating cell-to-cell communications. Exosomes have crucial roles in biological events such as intercellular communication, regulation of gene expression, apoptosis, inflammation, immunity, maturation and differentiation due to their inner composition, which includes nucleic acids, proteins, and lipids. We focus on the roles of exosomes in OA pathogenesis and discuss how they might be used in clinical practice for OA diagnosis and treatment. Our paper not only provides a comprehensive review of exosomes in OA but also contributes to the development efforts of diagnostic and therapeutic tools for OA.
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Affiliation(s)
- Hamza Malik Okuyan
- Department of Physiotherapy and Rehabilitation - Faculty of Health Sciences, Biomedical Technologies Application and Research Center, Physiotherapy and Rehabilitation Application and Research Center, Sakarya University of Applied Sciences, Sakarya, Türkiye.
| | - Ayça Coşkun
- Department of Physiotherapy and Rehabilitation - Faculty of Health Sciences, Physiotherapy and Rehabilitation Application and Research Center, Sakarya University of Applied Sciences, Sakarya, Türkiye
| | - Mehmet A Begen
- Department of Epidemiology and Biostatistics-Schulich School of Medicine and Dentistry, Ivey Business School, University of Western Ontario, London, ON, Canada
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3
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Martelo-Vidal L, Vázquez-Mera S, Miguéns-Suárez P, Bravo-López SB, Makrinioti H, Domínguez-Arca V, de-Miguel-Díez J, Gómez-Carballa A, Salas A, González-Barcala FJ, Salgado FJ, Nieto-Fontarigo JJ. Urinary Proteome and Exosome Analysis Protocol for the Discovery of Respiratory Diseases Biomarkers. Biomolecules 2025; 15:60. [PMID: 39858454 PMCID: PMC11762655 DOI: 10.3390/biom15010060] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Revised: 11/04/2024] [Accepted: 12/31/2024] [Indexed: 01/27/2025] Open
Abstract
This study aims to develop a protocol for respiratory disease-associated biomarker discovery by combining urine proteome studies with urinary exosome components analysis (i.e., miRNAs). To achieve this, urine was DTT treated to decrease uromodulin, then concentrated and ultracentrifuged. Proteomic analyses of exosome-free urine were performed using LC-MS/MS. Simultaneously, miRNA expression from urine exosomes was measured using either RTqPCR (pre-amplification) or nCounter Nanostring (non-amplication) analyses. We detected 548 different proteins in exosome-free urine samples (N = 5) with high confidence (FDR < 1%), many of them being expressed in different non-renal tissues. Specifically, lung-related proteins were overrepresented (Fold enrichment = 1.31; FDR = 0.0335) compared to whole human proteome, and 10-15% were already described as protein biomarkers for several pulmonary diseases. Urine proteins identified belong to several functional categories important in respiratory pathology. We could confirm the expression of miRNAs previously connected to respiratory diseases (i.e., miR-16-5p, miR-21-5p, miR-146a-5p, and miR-215-5p) in urine exosomes by RTqPCR. Finally, we detected 333 miRNAs using Nanostring, 15 of them up-regulated in T2high asthma (N = 4) compared to T2low asthma (N = 4) and healthy subjects (N = 4). Therefore, this protocol combining the urinary proteome (exosome free) with the study of urinary exosome components (i.e., miRNAs) holds great potential for molecular biomarker discovery of non-renal and particularly respiratory pathologies.
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Affiliation(s)
- Laura Martelo-Vidal
- BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; (L.M.-V.); (S.V.-M.); (P.M.-S.); (F.J.G.-B.); (J.J.N.-F.)
- Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Sara Vázquez-Mera
- BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; (L.M.-V.); (S.V.-M.); (P.M.-S.); (F.J.G.-B.); (J.J.N.-F.)
- Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Pablo Miguéns-Suárez
- BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; (L.M.-V.); (S.V.-M.); (P.M.-S.); (F.J.G.-B.); (J.J.N.-F.)
- Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Susana Belén Bravo-López
- Proteomic Service, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain;
| | - Heidi Makrinioti
- Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA;
| | - Vicente Domínguez-Arca
- Grupo de Física de Coloides y Polímeros, Departamento de Física de Partículas, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain;
- Bioprocess Engineering Group, Instituto de Investigacións Mariñas (IIM-CSIC), 36208 Vigo, Spain
| | - Javier de-Miguel-Díez
- Respiratory Department, Hospital General Universitario Gregorio Marañón, 28009 Madrid, Spain;
- Health Research Institute Gregorio Marañón (IISGM), 28009 Madrid, Spain
- Faculty of Medicine, Universidad Complutense de Madrid, 28040 Madrid, Spain
| | - Alberto Gómez-Carballa
- Genetics, Vaccines and Infections Research Group (GenViP), Instituto de Investigación Sanitaria de Santiago, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain; (A.G.-C.); (A.S.)
- Unidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
- Genética de Poblaciones en Biomedicina (GenPoB) Research Group, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), 15706 Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER-ES), 28029 Madrid, Spain
| | - Antonio Salas
- Genetics, Vaccines and Infections Research Group (GenViP), Instituto de Investigación Sanitaria de Santiago, Universidade de Santiago de Compostela, 15706 Santiago de Compostela, Spain; (A.G.-C.); (A.S.)
- Unidade de Xenética, Instituto de Ciencias Forenses, Facultade de Medicina, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
- Genética de Poblaciones en Biomedicina (GenPoB) Research Group, Instituto de Investigación Sanitaria (IDIS), Hospital Clínico Universitario de Santiago (SERGAS), 15706 Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBER-ES), 28029 Madrid, Spain
| | - Francisco Javier González-Barcala
- BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; (L.M.-V.); (S.V.-M.); (P.M.-S.); (F.J.G.-B.); (J.J.N.-F.)
- Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
- Department of Respiratory Medicine, University Hospital Complex of Santiago de Compostela, 15706 Santiago de Compostela, Spain
- Department of Medicine, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain
| | - Francisco Javier Salgado
- BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; (L.M.-V.); (S.V.-M.); (P.M.-S.); (F.J.G.-B.); (J.J.N.-F.)
- Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Juan José Nieto-Fontarigo
- BioLympho Research Group, Department of Biochemistry and Molecular Biology, Faculty of Biology-Biological Research Centre (CIBUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain; (L.M.-V.); (S.V.-M.); (P.M.-S.); (F.J.G.-B.); (J.J.N.-F.)
- Translational Research in Airway Diseases Group (TRIAD), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
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4
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Liu W, Wang X, Chen Y, Yuan J, Zhang H, Jin X, Jiang Y, Cao J, Wang Z, Yang S, Wang B, Wu T, Li J. Distinct molecular properties and functions of small EV subpopulations isolated from human umbilical cord MSCs using tangential flow filtration combined with size exclusion chromatography. J Extracell Vesicles 2025; 14:e70029. [PMID: 39783889 PMCID: PMC11714183 DOI: 10.1002/jev2.70029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Revised: 12/03/2024] [Accepted: 12/07/2024] [Indexed: 01/12/2025] Open
Abstract
As functional derivatives of mesenchymal stem cells (MSCs), small extracellular vesicles (sEVs) have garnered significant attention and application in regenerative medicine. However, the technical limitations for large-scale isolation of sEVs and their heterogeneous nature have added complexity to their applications. It remains unclear if the heterogeneous sEVs represent different aspects of MSCs functions. Here, we provide a method for the large-scale production of sEVs subpopulations derived from human umbilical cord mesenchymal stem cells (HucMSCs), utilizing tangential flow filtration combined with size exclusion chromatography. The resulting subpopulations, S1-sEVs and S2-sEVs, exhibited stable variations in size, membrane-marked proteins, and carrying cargos, thereby displaying distinct functions both in vitro and in animal disease models. S1-sEVs, that highly expressed CD9, HRS and GPC1, demonstrated a greater immunomodulatory impact, while S2-sEVs with enriched expression of CD63 and FLOT1/2 possessed enhanced capacities in promoting cell proliferation and angiogenesis. These discrepancies are attributed to the specific proteins and miRNAs they contain. Further investigation revealed that the two distinct sEVs subpopulations corresponded to different biological processes: the ESCRT pathway (S1-sEVs) and the ESCRT-independent pathway represented by lipid rafts (S2-sEVs). Therefore, we propose the potential for large-scale isolation and purification of sEVs subpopulations from HucMSCs with distinct functions. This approach may provide advantages for targeted therapeutic interventions in various MSC indications.
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Affiliation(s)
- Wei Liu
- State Key Laboratory of Reproductive Medicine and offspring healthNanjing Medical UniversityNanjingChina
- Reproductive Medicine Center, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Xinyu Wang
- State Key Laboratory of Reproductive Medicine and offspring healthNanjing Medical UniversityNanjingChina
| | - Yating Chen
- State Key Laboratory of Reproductive Medicine and offspring healthNanjing Medical UniversityNanjingChina
| | - Jiapei Yuan
- State Key Laboratory of Reproductive Medicine and offspring healthNanjing Medical UniversityNanjingChina
| | - Huiyu Zhang
- State Key Laboratory of Reproductive Medicine and offspring healthNanjing Medical UniversityNanjingChina
| | - Xin Jin
- Wuxi Maternity and Child Health Care HospitalAffiliated Women's Hospital of Jiangnan UniversityWuxiChina
| | - Yuying Jiang
- State Key Laboratory of Reproductive Medicine and offspring healthNanjing Medical UniversityNanjingChina
| | - Junjing Cao
- State Key Laboratory of Reproductive Medicine and offspring healthNanjing Medical UniversityNanjingChina
| | - Zibin Wang
- Center for Analysis and TestingNanjing Medical UniversityNanjingChina
| | - Shuo Yang
- State Key Laboratory of Reproductive Medicine and offspring healthNanjing Medical UniversityNanjingChina
- Department of Immunology, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Personalized Cancer Medicine, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical CenterNanjing Medical UniversityNanjingChina
| | - Bingwei Wang
- Department of PharmacologyNanjing University of Chinese MedicineNanjingChina
| | - Tinghe Wu
- Kornelis Bio‐pharmaceutical Company LimitedNanjingChina
| | - Jing Li
- State Key Laboratory of Reproductive Medicine and offspring healthNanjing Medical UniversityNanjingChina
- Innovation Center of Suzhou Nanjing Medical UniversitySuzhouChina
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5
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Oh C, Mazan-Mamczarz K, Gorospe M, Noh JH, Kim KM. Impact of UPF2 on the levels of CD81 on extracellular vesicles. Front Cell Dev Biol 2024; 12:1469080. [PMID: 39655046 PMCID: PMC11625909 DOI: 10.3389/fcell.2024.1469080] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2024] [Accepted: 10/29/2024] [Indexed: 12/12/2024] Open
Abstract
Extracellular vesicles (EVs) are involved in cell-to-cell communication. Following uptake, EV cargo molecules, including DNA, RNA, lipids, and proteins, influence gene expression and molecular signaling in recipient cells. Although various studies have identified disease-specific EV molecules, further research into their biogenesis and secretion mechanisms is needed for clinical application. Here, we investigated the role of UPF2 in regulating the biogenesis and components of EVs. Notably, UPF2 promoted the expression of CD81, a membrane protein marker of EVs, as UPF2 silencing decreased CD81 levels in EVs, both inside the cell and secreted. In contrast, the expression levels of CD63 increased, without altering the size or numbers of EVs. In addition, reducing UPF2 levels did not affect the total number of EVs but lowered production of CD81-positive EVs and reduced the efficiency of uptake by recipient cells. Collectively, our findings uncover a novel function for UPF2 in regulating the production of CD81 and changing EV properties.
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Affiliation(s)
- Chaehwan Oh
- Department of Biological Sciences, Chungnam National University, Daejeon, Republic of Korea
| | - Krystyna Mazan-Mamczarz
- Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States
| | - Myriam Gorospe
- Laboratory of Genetics and Genomics, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD, United States
| | - Ji Heon Noh
- Molecular Aging Biology Laboratory (MABL), Department of Biochemistry, College of Natural Science, Chungnam National University, Daejeon, Republic of Korea
| | - Kyoung Mi Kim
- Department of Biological Sciences, Chungnam National University, Daejeon, Republic of Korea
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6
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Pérez-Mato M, Dopico-López A, Akkoc Y, López-Amoedo S, Correa-Paz C, Candamo-Lourido M, Iglesias-Rey R, López-Arias E, Bugallo-Casal A, da Silva-Candal A, Bravo SB, Chantada-Vázquez MDP, Arias S, Santamaría-Cadavid M, Estany-Gestal A, Zaghmi A, Gauthier MA, Gutiérrez-Fernández M, Martin A, Llop J, Rodríguez C, Almeida Á, Migliavacca M, Polo E, Pelaz B, Gozuacik D, El Yamani N, SenGupta T, Rundén-Pran E, Vivancos J, Castellanos M, Díez-Tejedor E, Sobrino T, Rabinkov A, Mirelman D, Castillo J, Campos F. Preclinical validation of human recombinant glutamate-oxaloacetate transaminase for the treatment of acute ischemic stroke. iScience 2024; 27:111108. [PMID: 39524351 PMCID: PMC11543921 DOI: 10.1016/j.isci.2024.111108] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 08/21/2024] [Accepted: 10/02/2024] [Indexed: 11/16/2024] Open
Abstract
The blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use. We tested the pharmacokinetics and evaluated the protective efficacy of rGOT in rodent and non-human primate models that reflected clinical stroke conditions. We found that continuous intravenous administration of rGOT within the first 8 h after ischemic onset significantly reduced the infarct size in both severe (30%) and mild lesions (48%). Cerebrospinal fluid and proteomics analysis, in combination with positron emission tomography imaging, indicated that rGOT can reach the brain and induce cytoprotective autophagy and induce local protection by alleviating neuronal apoptosis. Our results suggest that rGOT can be safely used immediately in patients suspected of having a stroke. This study requires further validation in clinical stroke populations.
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Affiliation(s)
- María Pérez-Mato
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
- Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area of Hospital La Paz Institute for Health Research – IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), 28029 Madrid, Spain
| | - Antonio Dopico-López
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Yunus Akkoc
- Koç University Research Center for Translational Medicine (KUTTAM), Istanbul 34450, Turkey
- Department of Medical Biology, Koç University School of Medicine, Istanbul 34450, Turkey
| | - Sonia López-Amoedo
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Clara Correa-Paz
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - María Candamo-Lourido
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Ramón Iglesias-Rey
- Neuroimaging and Biotechnology Laboratory Group (NOBEL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Esteban López-Arias
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Ana Bugallo-Casal
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Andrés da Silva-Candal
- Neurology Service, University Hospital Complex of A Coruña, A Coruña Biomedical Research Institute, 15006 A Coruña, Spain
| | - Susana B. Bravo
- Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - María del Pilar Chantada-Vázquez
- Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
- Research Unit, Lucus Augusti University Hospital (HULA), Servizo Galego de Saúde (SERGAS), 27002 Lugo, Spain
| | - Susana Arias
- Stroke Unit, Department of Neurology, Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain
| | - María Santamaría-Cadavid
- Stroke Unit, Department of Neurology, Hospital Clínico Universitario, 15706 Santiago de Compostela, Spain
| | - Ana Estany-Gestal
- Unit of Methodology of the Research, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Ahlem Zaghmi
- Institut National de la Recherche Scientifique (INRS), EMT Research Center, Varennes, QC J3X 1S2, Canada
- Rheumatology Unit, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 171 77 Stockholm, Sweden
| | - Marc A. Gauthier
- Institut National de la Recherche Scientifique (INRS), EMT Research Center, Varennes, QC J3X 1S2, Canada
| | - María Gutiérrez-Fernández
- Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area of Hospital La Paz Institute for Health Research – IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), 28029 Madrid, Spain
| | - Abraham Martin
- Achucarro Basque Center for Neuroscience, 48940 Leioa, Spain
- Ikerbasque Basque Foundation for Science, 48009 Bilbao, Spain
| | - Jordi Llop
- CIC biomaGUNE, Basque Research and Technology Alliance (BRTA), 20014 San Sebastian, Spain
| | - Cristina Rodríguez
- Institute of Functional Biology and Genomics (IBFG), CSIC, University of Salamanca, 37007 Salamanca, Spain
- Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, CSIC, University of Salamanca, 37007 Salamanca, Spain
| | - Ángeles Almeida
- Institute of Functional Biology and Genomics (IBFG), CSIC, University of Salamanca, 37007 Salamanca, Spain
- Institute of Biomedical Research of Salamanca (IBSAL), University Hospital of Salamanca, CSIC, University of Salamanca, 37007 Salamanca, Spain
| | - Martina Migliavacca
- Center for Research in Biological Chemistry and Molecular Materials (CiQUS), University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
| | - Ester Polo
- Center for Research in Biological Chemistry and Molecular Materials (CiQUS), University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
| | - Beatriz Pelaz
- Center for Research in Biological Chemistry and Molecular Materials (CiQUS), University of Santiago de Compostela, 15705 Santiago de Compostela, Spain
| | - Devrim Gozuacik
- Koç University Research Center for Translational Medicine (KUTTAM), Istanbul 34450, Turkey
- Department of Medical Biology, Koç University School of Medicine, Istanbul 34450, Turkey
| | - Naouale El Yamani
- Health Effects Laboratory, Department for Environmental Chemistry, NILU-Norwegian Institute for Air Research, 2027 Kjeller, Norway
| | - Tanima SenGupta
- Health Effects Laboratory, Department for Environmental Chemistry, NILU-Norwegian Institute for Air Research, 2027 Kjeller, Norway
| | - Elise Rundén-Pran
- Health Effects Laboratory, Department for Environmental Chemistry, NILU-Norwegian Institute for Air Research, 2027 Kjeller, Norway
| | - José Vivancos
- Stroke Unit, Department of Neurology, Hospital Universitario de La Princesa & Instituto de Investigación Sanitaria La Princesa, 28006 Madrid, Spain
| | - Mar Castellanos
- Neurology Service, University Hospital Complex of A Coruña, A Coruña Biomedical Research Institute, 15006 A Coruña, Spain
| | - Exuperio Díez-Tejedor
- Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area of Hospital La Paz Institute for Health Research – IdiPAZ (La Paz University Hospital- Universidad Autónoma de Madrid), 28029 Madrid, Spain
| | - Tomás Sobrino
- NeuroAging Group (NEURAL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
- Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Aharon Rabinkov
- Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - David Mirelman
- Department of Biomolecular Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
| | - José Castillo
- Neuroimaging and Biotechnology Laboratory Group (NOBEL), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
| | - Francisco Campos
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain
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7
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Mehrvar A, Akbari M, Khosroshahi EM, Nekavand M, Mokhtari K, Baniasadi M, Aghababaian M, Karimi M, Amiri S, Moazen A, Maghsoudloo M, Alimohammadi M, Rahimzadeh P, Farahani N, Vaghar ME, Entezari M, Hashemi M. The impact of exosomes on bone health: A focus on osteoporosis. Pathol Res Pract 2024; 263:155618. [PMID: 39362132 DOI: 10.1016/j.prp.2024.155618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Revised: 09/24/2024] [Accepted: 09/25/2024] [Indexed: 10/05/2024]
Abstract
Osteoporosis is a widespread chronic condition. Although standard treatments are generally effective, they are frequently constrained by side effects and the risk of developing drug resistance. A promising area of research is the investigation of extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, which play a crucial role in bone metabolism. Exosomes, in particular, have shown significant potential in both the diagnosis and treatment of osteoporosis. EVs derived from osteoclasts, osteoblasts, mesenchymal stem cells, and other sources can influence bone metabolism, while exosomes from inflammatory and tumor cells may exacerbate bone loss, highlighting their dual role in osteoporosis pathology. This review offers a comprehensive overview of EV biogenesis, composition, and function in osteoporosis, focusing on their diagnostic and therapeutic potential. We examine the roles of various types of EVs and their cargo-proteins, RNAs, and lipids-in bone metabolism. Additionally, we explore the emerging applications of EVs as biomarkers and therapeutic agents, emphasizing the need for further research to address current challenges and enhance EV-based strategies for managing osteoporosis.
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Affiliation(s)
- Amir Mehrvar
- Assistant Professor, Department of Orthopedics, Taleghani Hospital Research Development Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammadarian Akbari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Elaheh Mohandesi Khosroshahi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Mehrandokht Nekavand
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Midwifery, Faculty of nursing and midwifery, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Khatere Mokhtari
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Mojtaba Baniasadi
- Department of Orthopedic Surgery, Isfahan University of Medical Sciences, Isfahan, Iran; MD, Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Department of Orthopedic, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Majid Aghababaian
- Department of Orthopedic Surgery, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mansour Karimi
- MD, Bone and Joint Reconstruction Research Center, Shafa Orthopedic Hospital, Department of Orthopedic, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Shayan Amiri
- MD, Assistant Professor of Orthopaedic Surgery, Shohadaye Haftom-e-Tir Hospital, Department of Orthopedic, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Alireza Moazen
- Department of Orthopedics, Bone and Joint Reconstruction Research Center, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Mazaher Maghsoudloo
- Key Laboratory of Epigenetics and Oncology, the Research Center for Preclinical Medicine, Southwest Medical University, Luzhou, Sichuan 646000, PR China
| | - Mina Alimohammadi
- Department of Immunology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Payman Rahimzadeh
- Surgical Research Society (SRS), Students' Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran.
| | - Najma Farahani
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Mohammad Eslami Vaghar
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of gynecology, Faculty of Medicine, Tehran Medical sciences, Islamic Azad University, Tehran, Iran.
| | - Maliheh Entezari
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
| | - Mehrdad Hashemi
- Farhikhtegan Medical Convergence Sciences Research Center, Farhikhtegan Hospital Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; Department of Genetics, Faculty of Advanced Science and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran.
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8
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Mondelo-Macía P, García-González J, León-Mateos L, Abalo A, Bravo S, Chantada Vazquez MDP, Muinelo-Romay L, López-López R, Díaz-Peña R, Dávila-Ibáñez AB. Identification of a Proteomic Signature for Predicting Immunotherapy Response in Patients With Metastatic Non-Small Cell Lung Cancer. Mol Cell Proteomics 2024; 23:100834. [PMID: 39216661 PMCID: PMC11474190 DOI: 10.1016/j.mcpro.2024.100834] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2023] [Revised: 08/17/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024] Open
Abstract
Immunotherapy has improved survival rates in patients with cancer, but identifying those who will respond to treatment remains a challenge. Advances in proteomic technologies have enabled the identification and quantification of nearly all expressed proteins in a single experiment. Integrating mass spectrometry with high-throughput technologies has facilitated comprehensive analysis of the plasma proteome in cancer, facilitating early diagnosis and personalized treatment. In this context, our study aimed to investigate the predictive and prognostic value of plasma proteome analysis using the SWATH-MS (Sequential Window Acquisition of All Theoretical Mass Spectra) strategy in newly diagnosed patients with non-small cell lung cancer (NSCLC) receiving pembrolizumab therapy. We enrolled 64 newly diagnosed patients with advanced NSCLC treated with pembrolizumab. Blood samples were collected from all patients before and during therapy. A total of 171 blood samples were analyzed using the SWATH-MS strategy. Plasma protein expression in metastatic NSCLC patients prior to receiving pembrolizumab was analyzed. A first cohort (discovery cohort) was employed to identify a proteomic signature predicting immunotherapy response. Thus, 324 differentially expressed proteins between responder and non-responder patients were identified. In addition, we developed a predictive model and found a combination of seven proteins, including ATG9A, DCDC2, HPS5, FIL1L, LZTL1, PGTA, and SPTN2, with stronger predictive value than PD-L1 expression alone. Additionally, survival analyses showed an association between the levels of ATG9A, DCDC2, SPTN2 and HPS5 with progression-free survival (PFS) and/or overall survival (OS). Our findings highlight the potential of proteomic technologies to detect predictive biomarkers in blood samples from NSCLC patients, emphasizing the correlation between immunotherapy response and the idenfied protein set.
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Affiliation(s)
- Patricia Mondelo-Macía
- Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain; Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain; Galician Precision Oncology Research Group (ONCOGAL), Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain
| | - Jorge García-González
- Department of Medical Oncology, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain; Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain; CIBERONC, Centro de Investigación Biomédica en Red Cáncer, Madrid, Spain
| | - Luis León-Mateos
- Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain; Galician Precision Oncology Research Group (ONCOGAL), Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain; Department of Medical Oncology, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain; Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain; CIBERONC, Centro de Investigación Biomédica en Red Cáncer, Madrid, Spain
| | - Alicia Abalo
- Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Susana Bravo
- Proteomic Unit, Instituto de Investigaciones Sanitarias-IDIS, Complejo Hospitalario Universitario de Santiago de Compostela (CHUS), Santiago de Compostela, Spain
| | - María Del Pilar Chantada Vazquez
- Proteomic Unit, Instituto de Investigaciones Sanitarias-IDIS, Complejo Hospitalario Universitario de Santiago de Compostela (CHUS), Santiago de Compostela, Spain
| | - Laura Muinelo-Romay
- Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain; Galician Precision Oncology Research Group (ONCOGAL), Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain; CIBERONC, Centro de Investigación Biomédica en Red Cáncer, Madrid, Spain
| | - Rafael López-López
- Liquid Biopsy Analysis Unit, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain; Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain; Galician Precision Oncology Research Group (ONCOGAL), Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain; Department of Medical Oncology, Complexo Hospitalario Universitario de Santiago de Compostela (SERGAS), Santiago de Compostela, Spain; Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain; CIBERONC, Centro de Investigación Biomédica en Red Cáncer, Madrid, Spain; Roche-Chus Joint Unit, Translational Medical Oncology Group, Oncomet, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain
| | - Roberto Díaz-Peña
- Fundación Pública Galega de Medicina Xenómica, SERGAS; Grupo de Medicina Xenomica-USC, Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain; Faculty of Health Sciences, Universidad Autónoma de Chile, Talca, Chile
| | - Ana B Dávila-Ibáñez
- Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain; CIBERONC, Centro de Investigación Biomédica en Red Cáncer, Madrid, Spain; Roche-Chus Joint Unit, Translational Medical Oncology Group, Oncomet, Health Research Institute of Santiago de Compostela (IDIS), Santiago de Compostela, Spain.
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9
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Kråkenes T, Sandvik CE, Ytterdal M, Gavasso S, Evjenth EC, Bø L, Kvistad CE. The Therapeutic Potential of Exosomes from Mesenchymal Stem Cells in Multiple Sclerosis. Int J Mol Sci 2024; 25:10292. [PMID: 39408622 PMCID: PMC11477223 DOI: 10.3390/ijms251910292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/17/2024] [Accepted: 09/23/2024] [Indexed: 10/20/2024] Open
Abstract
Although treatment for multiple sclerosis (MS) has undergone a revolution in the last decades, at least two important barriers remain: alleviation of innate inflammation driving disease progression and promotion of remyelination and neural regeneration. Mesenchymal stem cells (MSCs) possess immunomodulatory properties and promote remyelination in murine MS models. The main therapeutic mechanism has, however, been attributed to their potent paracrine capacity, and not to in vivo tissue implantation. Studies have demonstrated that exosomes released as part of the cells' secretome effectively encapsulate the beneficial properties of MSCs. These membrane-enclosed nanoparticles contain a variety of proteins and nucleic acids and serve as mediators of intercellular communication. In vitro studies have demonstrated that exosomes from MSCs modulate activated microglia from an inflammatory to an anti-inflammatory phenotype and thereby dampen the innate inflammation. Rodent studies have also demonstrated potent immunomodulation and remyelination with improved outcomes following exosome administration. Thus, exosomes from MSCs may represent a potential cell-free treatment modality to prevent disease progression and promote remyelination in MS. In this narrative review, we summarize the current knowledge of exosomes from MSCs as a potential treatment for MS and discuss the remaining issues before successful translation into clinical trials.
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Affiliation(s)
- Torbjørn Kråkenes
- Neuro-SysMed, Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway (L.B.); (C.E.K.)
| | - Casper Eugen Sandvik
- Department of Clinical Medicine, Faculty of Medicine, University of Bergen, 5021 Bergen, Norway
| | - Marie Ytterdal
- Neuro-SysMed, Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway (L.B.); (C.E.K.)
| | - Sonia Gavasso
- Neuro-SysMed, Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway (L.B.); (C.E.K.)
- Department of Clinical Medicine, Faculty of Medicine, University of Bergen, 5021 Bergen, Norway
| | - Elisabeth Claire Evjenth
- Neuro-SysMed, Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway (L.B.); (C.E.K.)
| | - Lars Bø
- Neuro-SysMed, Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway (L.B.); (C.E.K.)
- Department of Clinical Medicine, Faculty of Medicine, University of Bergen, 5021 Bergen, Norway
| | - Christopher Elnan Kvistad
- Neuro-SysMed, Department of Neurology, Haukeland University Hospital, 5021 Bergen, Norway (L.B.); (C.E.K.)
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10
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Smirnova O, Efremov Y, Klyucherev T, Peshkova M, Senkovenko A, Svistunov A, Timashev P. Direct and cell-mediated EV-ECM interplay. Acta Biomater 2024; 186:63-84. [PMID: 39043290 DOI: 10.1016/j.actbio.2024.07.029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 07/07/2024] [Accepted: 07/17/2024] [Indexed: 07/25/2024]
Abstract
Extracellular vesicles (EV) are a heterogeneous group of lipid particles excreted by cells. They play an important role in regeneration, development, inflammation, and cancer progression, together with the extracellular matrix (ECM), which they constantly interact with. In this review, we discuss direct and indirect interactions of EVs and the ECM and their impact on different physiological processes. The ECM affects the secretion of EVs, and the properties of the ECM and EVs modulate EVs' diffusion and adhesion. On the other hand, EVs can affect the ECM both directly through enzymes and indirectly through the modulation of the ECM synthesis and remodeling by cells. This review emphasizes recently discovered types of EVs bound to the ECM and isolated by enzymatic digestion, including matrix-bound nanovesicles (MBV) and tissue-derived EV (TiEV). In addition to the experimental studies, computer models of the EV-ECM-cell interactions, from all-atom models to quantitative pharmacology models aiming to improve our understanding of the interaction mechanisms, are also considered. STATEMENT OF SIGNIFICANCE: Application of extracellular vesicles in tissue engineering is an actively developing area. Vesicles not only affect cells themselves but also interact with the matrix and change it. The matrix also influences both cells and vesicles. In this review, different possible types of interactions between vesicles, matrix, and cells are discussed. Furthermore, the united EV-ECM system and its regulation through the cellular activity are presented.
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Affiliation(s)
- Olga Smirnova
- Institute for Regenerative Medicine, Sechenov University, 119991 Moscow, Russia
| | - Yuri Efremov
- Institute for Regenerative Medicine, Sechenov University, 119991 Moscow, Russia
| | - Timofey Klyucherev
- Institute for Regenerative Medicine, Sechenov University, 119991 Moscow, Russia
| | - Maria Peshkova
- Institute for Regenerative Medicine, Sechenov University, 119991 Moscow, Russia; World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov University, 119991 Moscow, Russia
| | - Alexey Senkovenko
- Institute for Regenerative Medicine, Sechenov University, 119991 Moscow, Russia
| | | | - Peter Timashev
- Institute for Regenerative Medicine, Sechenov University, 119991 Moscow, Russia; World-Class Research Center "Digital Biodesign and Personalized Healthcare", Sechenov University, 119991 Moscow, Russia; Chemistry Department, Lomonosov Moscow State University, 119991 Moscow, Russia.
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11
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Athira AP, Sreekanth S, Chandran A, Lahon A. Dual Role of Extracellular Vesicles as Orchestrators of Emerging and Reemerging Virus Infections. Cell Biochem Biophys 2024:10.1007/s12013-024-01495-3. [PMID: 39225901 DOI: 10.1007/s12013-024-01495-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/21/2024] [Indexed: 09/04/2024]
Abstract
Current decade witnessed the emergence and re-emergence of many viruses, which affected public health significantly. Viruses mainly utilize host cell machinery to promote its growth, and spread of these diseases. Numerous factors influence virus-host cell interactions, of which extracellular vesicles play an important role, where they transfer information both locally and distally by enclosing viral and host-derived proteins and RNAs as their cargo. Thus, they play a dual role in mediating virus infections by promoting virus dissemination and evoking immune responses in host organisms. Moreover, it acts as a double-edged sword during these infections. Advances in extracellular vesicles regulating emerging and reemerging virus infections, particularly in the context of SARS-CoV-2, Dengue, Ebola, Zika, Chikungunya, West Nile, and Japanese Encephalitis viruses are discussed in this review.
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Affiliation(s)
- A P Athira
- Department of Viral Vaccines, Institute of Advanced Virology, Bio 360 Life Science Park, Thiruvananthapuram, Kerala, India
| | - Smrithi Sreekanth
- Department of Viral Vaccines, Institute of Advanced Virology, Bio 360 Life Science Park, Thiruvananthapuram, Kerala, India
| | - Ananthu Chandran
- Department of Viral Vaccines, Institute of Advanced Virology, Bio 360 Life Science Park, Thiruvananthapuram, Kerala, India
| | - Anismrita Lahon
- Department of Viral Vaccines, Institute of Advanced Virology, Bio 360 Life Science Park, Thiruvananthapuram, Kerala, India.
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12
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Parvin A, Erabi G, Mohammadpour D, Maleki-Kakelar H, Sadeghpour S, Pashaei MR, Taheri-Anganeh M, Ghasemnejad-Berenji H. Infertility: Focus on the therapeutic potential of extracellular vesicles. Reprod Biol 2024; 24:100925. [PMID: 39018753 DOI: 10.1016/j.repbio.2024.100925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2024] [Revised: 05/28/2024] [Accepted: 07/05/2024] [Indexed: 07/19/2024]
Abstract
Infertility is a well-known problem that arises from a variety of reproductive diseases. Until now, researchers have tried various methods to restore fertility, including medication specific to the cause, hormone treatments, surgical removals, and assisted reproductive technologies. While these methods do produce results, they do not consistently lead to fertility restoration in every instance. The use of exosome therapy has significant potential in treating infertility in patients. This is because exosomes, microvesicles, and apoptotic bodies, which are different types of vesicles, play a crucial role in transferring bioactive molecules that aid in cell-to-cell communication. Reproductive fluids can transport a variety of molecular cargos, such as miRNAs, mRNAs, proteins, lipids, and DNA molecules. The percentage of these cargos in the fluids can be linked to their physiological and pathological status. EVs are involved in several physiological and pathological processes and offer interesting non-cellular therapeutic possibilities to treat infertility. EVs (extracellular vesicles) transplantation has been shown in many studies to be a key part of regenerating different parts of the reproductive system, including the production of oocytes and the start of sperm production. Nevertheless, the existing evidence necessitates testifying to the effectiveness of injecting EVs in resolving reproductive problems among humans. This review focuses on the current literature about infertility issues in both females and males, specifically examining the potential treatments involving extracellular vesicles (EVs).
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Affiliation(s)
- Ali Parvin
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Gisou Erabi
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Donna Mohammadpour
- Student Research Committee, Urmia University of Medical Sciences, Urmia, Iran
| | - Hadi Maleki-Kakelar
- Solid Tumor Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran
| | - Sonia Sadeghpour
- Reproductive Health Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran; Department of Obstetrics & Gynecology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Mohammad Reza Pashaei
- Department of Internal Medicine, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran
| | - Mortaza Taheri-Anganeh
- Cellular and Molecular Research Center, Cellular and Molecular Medicine Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
| | - Hojat Ghasemnejad-Berenji
- Reproductive Health Research Center, Clinical Research Institute, Urmia University of Medical Sciences, Urmia, Iran.
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13
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Putthanbut N, Lee JY, Borlongan CV. Extracellular vesicle therapy in neurological disorders. J Biomed Sci 2024; 31:85. [PMID: 39183263 PMCID: PMC11346291 DOI: 10.1186/s12929-024-01075-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2024] [Accepted: 08/16/2024] [Indexed: 08/27/2024] Open
Abstract
Extracellular vesicles (EVs) are vital for cell-to-cell communication, transferring proteins, lipids, and nucleic acids in various physiological and pathological processes. They play crucial roles in immune modulation and tissue regeneration but are also involved in pathogenic conditions like inflammation and degenerative disorders. EVs have heterogeneous populations and cargo, with numerous subpopulations currently under investigations. EV therapy shows promise in stimulating tissue repair and serving as a drug delivery vehicle, offering advantages over cell therapy, such as ease of engineering and minimal risk of tumorigenesis. However, challenges remain, including inconsistent nomenclature, complex characterization, and underdeveloped large-scale production protocols. This review highlights the recent advances and significance of EVs heterogeneity, emphasizing the need for a better understanding of their roles in disease pathologies to develop tailored EV therapies for clinical applications in neurological disorders.
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Affiliation(s)
- Napasiri Putthanbut
- Department of Neurosurgery, Center of Aging and Brain Repair, University of South Florida, Tampa, USA
- Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Salaya, Thailand
| | - Jea Young Lee
- Department of Neurosurgery, Center of Aging and Brain Repair, University of South Florida, Tampa, USA
| | - Cesario V Borlongan
- Department of Neurosurgery, Center of Aging and Brain Repair, University of South Florida, Tampa, USA.
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14
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Kurup AJ, Bailet F, Fürthauer M. Myosin1G promotes Nodal signaling to control zebrafish left-right asymmetry. Nat Commun 2024; 15:6547. [PMID: 39095343 PMCID: PMC11297164 DOI: 10.1038/s41467-024-50868-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Accepted: 07/22/2024] [Indexed: 08/04/2024] Open
Abstract
Myosin1D (Myo1D) has recently emerged as a conserved regulator of animal Left-Right (LR) asymmetry that governs the morphogenesis of the vertebrate central LR Organizer (LRO). In addition to Myo1D, the zebrafish genome encodes the closely related Myo1G. Here we show that while Myo1G also controls LR asymmetry, it does so through an entirely different mechanism. Myo1G promotes the Nodal-mediated transfer of laterality information from the LRO to target tissues. At the cellular level, Myo1G is associated with endosomes positive for the TGFβ signaling adapter SARA. myo1g mutants have fewer SARA-positive Activin receptor endosomes and a reduced responsiveness to Nodal ligands that results in a delay of left-sided Nodal propagation and tissue-specific laterality defects in organs that are most distant from the LRO. Additionally, Myo1G promotes signaling by different Nodal ligands in specific biological contexts. Our findings therefore identify Myo1G as a context-dependent regulator of the Nodal signaling pathway.
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15
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Albakova Z. HSP90 multi-functionality in cancer. Front Immunol 2024; 15:1436973. [PMID: 39148727 PMCID: PMC11324539 DOI: 10.3389/fimmu.2024.1436973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 07/18/2024] [Indexed: 08/17/2024] Open
Abstract
The 90-kDa heat shock proteins (HSP90s) are molecular chaperones essential for folding, unfolding, degradation and activity of a wide range of client proteins. HSP90s and their cognate co-chaperones are subject to various post-translational modifications, functional consequences of which are not fully understood in cancer. Intracellular and extracellular HSP90 family members (HSP90α, HSP90β, GRP94 and TRAP1) promote cancer by sustaining various hallmarks of cancer, including cell death resistance, replicative immortality, tumor immunity, angiogenesis, invasion and metastasis. Given the importance of HSP90 in tumor progression, various inhibitors and HSP90-based vaccines were developed for the treatment of cancer. Further understanding of HSP90 functions in cancer may provide new opportunities and novel therapeutic strategies for the treatment of cancer.
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Affiliation(s)
- Zarema Albakova
- Department of Biology, Lomonosov Moscow State University, Moscow, Russia
- Chokan Limited Liability Partnership, Almaty, Kazakhstan
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16
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Candamo-Lourido M, Dopico-López A, López-Arias E, López-Amoedo S, Correa-Paz C, Chantada-Vázquez MP, Bugallo-Casal A, del Pozo-Filíu L, Pérez-Gayol L, Palomar-Alonso N, Bravo SB, Campos F, Pérez-Mato M. Comparative Brain Proteomic Analysis between Sham and Cerebral Ischemia Experimental Groups. Int J Mol Sci 2024; 25:7538. [PMID: 39062782 PMCID: PMC11277324 DOI: 10.3390/ijms25147538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Revised: 07/05/2024] [Accepted: 07/05/2024] [Indexed: 07/28/2024] Open
Abstract
Sham control groups are essential in experimental animal studies to reduce the influence of surgical intervention. The intraluminal filament procedure is one of the most common models of middle cerebral artery occlusion (MCAO) used in the study of brain ischemia. However, a sham group is usually not included in the experimental design of these studies. In this study, we aimed to evaluate the relevance of the sham group by analyzing and comparing the brain protein profiles of the sham and MCAO groups. In the sham group, 98 dysregulated proteins were detected, compared to 171 in the ischemic group. Moreover, a comparative study of protein profiles revealed the existence of a pool of 57 proteins that appeared to be dysregulated in both sham and ischemic animals. These results indicated that the surgical procedure required for the intraluminal occlusion of the middle cerebral artery (MCA) induces changes in brain protein expression that are not associated with ischemic lesions. This study highlights the importance of including sham control groups in the experimental design, to ensure that surgical intervention does not affect the therapeutic target under study.
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Affiliation(s)
- María Candamo-Lourido
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (M.C.-L.); (A.D.-L.); (E.L.-A.); (S.L.-A.); (C.C.-P.); (A.B.-C.); (L.P.-G.); (N.P.-A.)
| | - Antonio Dopico-López
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (M.C.-L.); (A.D.-L.); (E.L.-A.); (S.L.-A.); (C.C.-P.); (A.B.-C.); (L.P.-G.); (N.P.-A.)
| | - Esteban López-Arias
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (M.C.-L.); (A.D.-L.); (E.L.-A.); (S.L.-A.); (C.C.-P.); (A.B.-C.); (L.P.-G.); (N.P.-A.)
| | - Sonia López-Amoedo
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (M.C.-L.); (A.D.-L.); (E.L.-A.); (S.L.-A.); (C.C.-P.); (A.B.-C.); (L.P.-G.); (N.P.-A.)
| | - Clara Correa-Paz
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (M.C.-L.); (A.D.-L.); (E.L.-A.); (S.L.-A.); (C.C.-P.); (A.B.-C.); (L.P.-G.); (N.P.-A.)
| | - María Pilar Chantada-Vázquez
- Proteomic Unit, Research Institute of Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS), 15706 Santiago de Compostela, Spain; (M.P.C.-V.); (S.B.B.)
| | - Ana Bugallo-Casal
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (M.C.-L.); (A.D.-L.); (E.L.-A.); (S.L.-A.); (C.C.-P.); (A.B.-C.); (L.P.-G.); (N.P.-A.)
| | - Lucía del Pozo-Filíu
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (M.C.-L.); (A.D.-L.); (E.L.-A.); (S.L.-A.); (C.C.-P.); (A.B.-C.); (L.P.-G.); (N.P.-A.)
| | - Lara Pérez-Gayol
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (M.C.-L.); (A.D.-L.); (E.L.-A.); (S.L.-A.); (C.C.-P.); (A.B.-C.); (L.P.-G.); (N.P.-A.)
| | - Nuria Palomar-Alonso
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (M.C.-L.); (A.D.-L.); (E.L.-A.); (S.L.-A.); (C.C.-P.); (A.B.-C.); (L.P.-G.); (N.P.-A.)
| | - Susana B. Bravo
- Proteomic Unit, Research Institute of Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago de Compostela (CHUS), 15706 Santiago de Compostela, Spain; (M.P.C.-V.); (S.B.B.)
| | - Francisco Campos
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (M.C.-L.); (A.D.-L.); (E.L.-A.); (S.L.-A.); (C.C.-P.); (A.B.-C.); (L.P.-G.); (N.P.-A.)
| | - María Pérez-Mato
- Translational Stroke Laboratory Group (TREAT), Clinical Neurosciences Research Laboratory (LINC), Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain; (M.C.-L.); (A.D.-L.); (E.L.-A.); (S.L.-A.); (C.C.-P.); (A.B.-C.); (L.P.-G.); (N.P.-A.)
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17
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Shi M, Jia JS, Gao GS, Hua X. Advances and challenges of exosome-derived noncoding RNAs for hepatocellular carcinoma diagnosis and treatment. Biochem Biophys Rep 2024; 38:101695. [PMID: 38560049 PMCID: PMC10979073 DOI: 10.1016/j.bbrep.2024.101695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 02/10/2024] [Accepted: 03/20/2024] [Indexed: 04/04/2024] Open
Abstract
Exosomes, also termed extracellular vesicles (EVs), are an important component of the tumor microenvironment (TME) and exert versatile effects on the molecular communications in the TME of hepatocellular carcinoma (HCC). Exosome-mediated intercellular communication is closely associated with the tumorigenesis and development of HCC. Exosomes can be extracted through ultracentrifugation and size exclusion, followed by molecular analysis through sequencing. Increasing studies have confirmed the important roles of exosome-derived ncRNAs in HCC, including tumorigenesis, progression, immune escape, and treatment resistance. Due to the protective membrane structure of exosomes, the ncRNAs carried by exosomes can evade degradation by enzymes in body fluids and maintain good expression stability. Thus, exosome-derived ncRNAs are highly suitable as biomarkers for the diagnosis and prognostic prediction of HCC, such as exosomal miR-21-5p, miR-221-3p and lncRNA-ATB. In addition, substantial studies revealed that the up-or down-regulation of exosome-derived ncRNAs had an important impact on HCC progression and response to treatment. Exosomal biomarkers, such as miR-23a, lncRNA DLX6-AS1, miR-21-5p, lncRNA TUC339, lncRNA HMMR-AS1 and hsa_circ_0004658, can reshape immune microenvironment by regulating M2-type macrophage polarization and then promote HCC development. Therefore, by controlling exosome biogenesis and modulating exosomal ncRNA levels, HCC may be inhibited or eliminated. In this current review, we summarized the recent findings on the role of exosomes in HCC progression and analyzed the relationship between exosome-derived ncRNAs and HCC diagnosis and treatment.
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Affiliation(s)
- Min Shi
- Department of Clinical Laboratory, Ningbo No.2 Hospital, Ningbo, Zhejiang, China
| | - Jun-Su Jia
- Department of Clinical Laboratory, Ningbo No.2 Hospital, Ningbo, Zhejiang, China
| | - Guo-Sheng Gao
- Department of Clinical Laboratory, Ningbo No.2 Hospital, Ningbo, Zhejiang, China
| | - Xin Hua
- Department of Clinical Laboratory, Ningbo No.2 Hospital, Ningbo, Zhejiang, China
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18
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Wardhani K, Levina A, Grau GER, Lay PA. Fluorescent, phosphorescent, magnetic resonance contrast and radioactive tracer labelling of extracellular vesicles. Chem Soc Rev 2024; 53:6779-6829. [PMID: 38828885 DOI: 10.1039/d2cs00238h] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/05/2024]
Abstract
This review focusses on the significance of fluorescent, phosphorescent labelling and tracking of extracellular vesicles (EVs) for unravelling their biology, pathophysiology, and potential diagnostic and therapeutic uses. Various labeling strategies, such as lipid membrane, surface protein, luminal, nucleic acid, radionuclide, quantum dot labels, and metal complex-based stains, are evaluated for visualizing and characterizing EVs. Direct labelling with fluorescent lipophilic dyes is simple but generally lacks specificity, while surface protein labelling offers selectivity but may affect EV-cell interactions. Luminal and nucleic acid labelling strategies have their own advantages and challenges. Each labelling approach has strengths and weaknesses, which require a suitable probe and technique based on research goals, but new tetranuclear polypyridylruthenium(II) complexes as phosphorescent probes have strong phosphorescence, selective staining, and stability. Future research should prioritize the design of novel fluorescent probes and labelling platforms that can significantly enhance the efficiency, accuracy, and specificity of EV labeling, while preserving their composition and functionality. It is crucial to reduce false positive signals and explore the potential of multimodal imaging techniques to gain comprehensive insights into EVs.
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Affiliation(s)
- Kartika Wardhani
- School of Chemistry, The University of Sydney, Sydney, New South Wales, 2006, Australia.
- Biochemistry and Biotechnology (B-TEK) Group, Bioscience Division, Los Alamos National Laboratory, Los Alamos, New Mexico, 87545, USA
| | - Aviva Levina
- School of Chemistry, The University of Sydney, Sydney, New South Wales, 2006, Australia.
| | - Georges E R Grau
- Sydney Nano, The University of Sydney, Sydney, New South Wales, 2006, Australia
- Sydney Cancer Network, The University of Sydney, Sydney, New South Wales, 2006, Australia
- Marie Bashir Institute, The University of Sydney, Sydney, New South Wales, 2006, Australia
- Vascular Immunology Unit, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, 2006, Australia
| | - Peter A Lay
- School of Chemistry, The University of Sydney, Sydney, New South Wales, 2006, Australia.
- Sydney Nano, The University of Sydney, Sydney, New South Wales, 2006, Australia
- Sydney Cancer Network, The University of Sydney, Sydney, New South Wales, 2006, Australia
- Marie Bashir Institute, The University of Sydney, Sydney, New South Wales, 2006, Australia
- Sydney Analytical, The University of Sydney, Sydney, New South Wales, 2006, Australia
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19
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René CA, Parks RJ. Bioengineering extracellular vesicle cargo for optimal therapeutic efficiency. Mol Ther Methods Clin Dev 2024; 32:101259. [PMID: 38770107 PMCID: PMC11103572 DOI: 10.1016/j.omtm.2024.101259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/22/2024]
Abstract
Extracellular vesicles (EVs) have the innate ability to carry proteins, lipids, and nucleic acids between cells, and thus these vesicles have gained much attention as potential therapeutic delivery vehicles. Many strategies have been explored to enhance the loading of specific cargoes of interest into EVs, which could result in the delivery of more therapeutic to recipient cells, thus enhancing therapeutic efficacy. In this review, we discuss the natural biogenesis of EVs, the mechanism by which proteins and nucleic acids are selected for inclusion in EVs, and novel methods that have been employed to enhance loading of specific cargoes into EVs. As well, we discuss biodistribution of administered EVs in vivo and summarize clinical trials that have attempted to harness the therapeutic potential of EVs.
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Affiliation(s)
- Charlotte A. René
- Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
- Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON K1H 8M5, Canada
| | - Robin J. Parks
- Regenerative Medicine Program, Ottawa Hospital Research Institute, Ottawa, ON K1H 8L6, Canada
- Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Centre for Neuromuscular Disease, University of Ottawa, Ottawa, ON K1H 8M5, Canada
- Department of Medicine, The Ottawa Hospital and University of Ottawa, Ottawa, ON K1H 8L6, Canada
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20
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He R, Chen Y. The Role of Adipose Tissue-derived Exosomes in Chronic Metabolic Disorders. Curr Med Sci 2024; 44:463-474. [PMID: 38900388 DOI: 10.1007/s11596-024-2902-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2023] [Accepted: 05/28/2024] [Indexed: 06/21/2024]
Abstract
Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases, such as type 2 diabetes mellitus (T2DM), cardiovascular diseases, and non-alcoholic fatty liver disease (NAFLD). Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles (EVs) that play a role in the regulation of whole-body metabolism. Exosomes are a subtype of EVs, and accumulating evidence indicates that adipose tissue exosomes (AT Exos) mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms. However, the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated. In this review, we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders. Moreover, we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.
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Affiliation(s)
- Rui He
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
- Laboratory of Endocrinology & Metabolism, Key Laboratory of Vascular Aging of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
| | - Yong Chen
- Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Laboratory of Endocrinology & Metabolism, Key Laboratory of Vascular Aging of the Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
- Branch of National Clinical Research Center for Metabolic Diseases, Wuhan, 430030, China.
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21
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Mohammadi A, Shabani R, Bashiri Z, Rafiei S, Asgari H, Koruji M. Therapeutic potential of exosomes in spermatogenesis regulation and male infertility. Biol Cell 2024; 116:e2300127. [PMID: 38593304 DOI: 10.1111/boc.202300127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Revised: 02/19/2024] [Accepted: 02/22/2024] [Indexed: 04/11/2024]
Abstract
BACKGROUND Spermatogenesis is a fundamental process crucial for male reproductive health and fertility. Exosomes, small membranous vesicles released by various cell types, have recently garnered attention for their role in intercellular communication. OBJECTIVE This review aims to comprehensively explore the role of exosomes in regulating spermatogenesis, focusing on their involvement in testicular development and cell-to-cell communication. METHODS A systematic examination of literature was conducted to gather relevant studies elucidating the biogenesis, composition, and functions of exosomes in the context of spermatogenesis. RESULTS Exosomes play a pivotal role in orchestrating the complex signaling networks required for proper spermatogenesis. They facilitate the transfer of key regulatory molecules between different cell populations within the testes, including Sertoli cells, Leydig cells, and germ cells. CONCLUSION The emerging understanding of exosome-mediated communication sheds light on novel mechanisms underlying spermatogenesis regulation. Further research in this area holds promise for insights into male reproductive health and potential therapeutic interventions.
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Affiliation(s)
- Amirhossein Mohammadi
- Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Ronak Shabani
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Reproductive Sciences and Technology Research Center, Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Zahra Bashiri
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
- Endometrium and Endometriosis Research Center, Hamadan University of Medical Sciences, Hamadan, Iran
- Omid Fertility & Infertility Clinic, Hamedan, Iran
| | - Sara Rafiei
- Department of Botany and Plant Sciences, Faculty of Biological Sciences, Alzahra University, Tehran, Iran
| | - Hamidreza Asgari
- Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Morteza Koruji
- Stem Cell and Regenerative Medicine Research Center, Iran University of Medical Sciences, Tehran, Iran
- Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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22
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Aragón-Herrera A, Feijóo-Bandín S, Vázquez-Abuín X, Anido-Varela L, Moraña-Fernández S, Bravo SB, Tarazón E, Roselló-Lletí E, Portolés M, García-Seara J, Seijas J, Rodríguez-Penas D, Bani D, Gualillo O, González-Juanatey JR, Lago F. Human recombinant relaxin-2 (serelaxin) regulates the proteome, lipidome, lipid metabolism and inflammatory profile of rat visceral adipose tissue. Biochem Pharmacol 2024; 223:116157. [PMID: 38518995 DOI: 10.1016/j.bcp.2024.116157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2024] [Revised: 03/19/2024] [Accepted: 03/19/2024] [Indexed: 03/24/2024]
Abstract
Recombinant human relaxin-2 (serelaxin) has been widely proven as a novel drug with myriad effects at different cardiovascular levels, which support its potential therapeutic efficacy in several cardiovascular diseases (CVD). Considering these effects, together with the influence of relaxin-2 on adipocyte physiology and adipokine secretion, and the connection between visceral adipose tissue (VAT) dysfunction and the development of CVD, we could hypothesize that relaxin-2 may regulate VAT metabolism. Our objective was to evaluate the impact of a 2-week serelaxin treatment on the proteome and lipidome of VAT from Sprague-Dawley rats. We found that serelaxin increased 1 polyunsaturated fatty acid and 6 lysophosphatidylcholines and decreased 4 triglycerides in VAT employing ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) based platforms, and that regulates 47 phosphoproteins using SWATH/MS analysis. Through RT-PCR, we found that serelaxin treatment also caused an effect on VAT lipolysis through an increase in the mRNA expression of hormone-sensitive lipase (HSL) and a decrease in the expression of adipose triglyceride lipase (ATGL), together with a reduction in the VAT expression of the fatty acid transporter cluster of differentiation 36 (Cd36). Serelaxin also caused an anti-inflammatory effect in VAT by the decrease in the mRNA expression of tumor necrosis factor α (TNFα), interleukin-1β (IL-1β), chemerin, and its receptor. In conclusion, our results highlight the regulatory role of serelaxin in the VAT proteome and lipidome, lipolytic function, and inflammatory profile, suggesting the implication of several mechanisms supporting the potential benefit of serelaxin for the prevention of obesity and metabolic disorders.
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Affiliation(s)
- Alana Aragón-Herrera
- Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain.
| | - Sandra Feijóo-Bandín
- Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
| | - Xocas Vázquez-Abuín
- Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - Laura Anido-Varela
- Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
| | - Sandra Moraña-Fernández
- Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Group, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - Susana B Bravo
- Proteomics Unit, Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain
| | - Estefanía Tarazón
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain; Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain
| | - Esther Roselló-Lletí
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain; Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain
| | - Manuel Portolés
- Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain; Cardiocirculatory Unit, Health Research Institute of La Fe University Hospital, Valencia, Spain
| | - Javier García-Seara
- Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain; Arrhytmia Unit, Cardiology Department, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS, Universidade de Santiago de Compostela, Santiago de Compostela, Spain
| | - José Seijas
- Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain; Cardiology Department Clinical Trial Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - Diego Rodríguez-Penas
- Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Department Clinical Trial Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - Daniele Bani
- Research Unit of Histology & Embryology, Department of Experimental & Clinical Medicine, University of Florence, Florence, Italy
| | - Oreste Gualillo
- Laboratory of Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - José Ramón González-Juanatey
- Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain; Department of Psychiatry, Radiology, Public Health, Nursing and Medicine, IDIS, Universidade de Santiago de Compostela, Santiago de Compostela, Spain; Cardiology Department, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain
| | - Francisca Lago
- Cellular and Molecular Cardiology Research Unit, IDIS, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, Madrid, Spain
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23
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Cui L, Zheng J, Lu Y, Lin P, Lin Y, Zheng Y, Xu R, Mai Z, Guo B, Zhao X. New frontiers in salivary extracellular vesicles: transforming diagnostics, monitoring, and therapeutics in oral and systemic diseases. J Nanobiotechnology 2024; 22:171. [PMID: 38610017 PMCID: PMC11015696 DOI: 10.1186/s12951-024-02443-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2023] [Accepted: 03/28/2024] [Indexed: 04/14/2024] Open
Abstract
Salivary extracellular vesicles (EVs) have emerged as key tools for non-invasive diagnostics, playing a crucial role in the early detection and monitoring of diseases. These EVs surpass whole saliva in biomarker detection due to their enhanced stability, which minimizes contamination and enzymatic degradation. The review comprehensively discusses methods for isolating, enriching, quantifying, and characterizing salivary EVs. It highlights their importance as biomarkers in oral diseases like periodontitis and oral cancer, and underscores their potential in monitoring systemic conditions. Furthermore, the review explores the therapeutic possibilities of salivary EVs, particularly in personalized medicine through engineered EVs for targeted drug delivery. The discussion also covers the current challenges and future prospects in the field, emphasizing the potential of salivary EVs in advancing clinical practice and disease management.
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Affiliation(s)
- Li Cui
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Jiarong Zheng
- Department of Dentistry, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Ye Lu
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Pei Lin
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Yunfan Lin
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Yucheng Zheng
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Rongwei Xu
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Zizhao Mai
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China
| | - Bing Guo
- Department of Dentistry, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China
| | - Xinyuan Zhao
- Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, Guangdong, 510280, China.
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24
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El Safadi D, Mokhtari A, Krejbich M, Lagrave A, Hirigoyen U, Lebeau G, Viranaicken W, Krejbich-Trotot P. Exosome-Mediated Antigen Delivery: Unveiling Novel Strategies in Viral Infection Control and Vaccine Design. Vaccines (Basel) 2024; 12:280. [PMID: 38543914 PMCID: PMC10974137 DOI: 10.3390/vaccines12030280] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 03/01/2024] [Accepted: 03/04/2024] [Indexed: 01/03/2025] Open
Abstract
Exosomes are small subtypes of extracellular vesicles (EVs) naturally released by different types of cells into their environment. Their physiological roles appear to be multiple, yet many aspects of their biological activities remain to be understood. These vesicles can transport and deliver a variety of cargoes and may serve as unconventional secretory vesicles. Thus, they play a crucial role as important vectors for intercellular communication and the maintenance of homeostasis. Exosome production and content can vary under several stresses or modifications in the cell microenvironment, influencing cellular responses and stimulating immunity. During infectious processes, exosomes are described as double-edged swords, displaying both beneficial and detrimental effects. Owing to their tractability, the analysis of EVs from multiple biofluids has become a booming tool for monitoring various pathologies, from infectious to cancerous origins. In this review, we present an overview of exosome features and discuss their particular and ambiguous functions in infectious contexts. We then focus on their properties as diagnostic or therapeutic tools. In this regard, we explore the capacity of exosomes to vectorize immunogenic viral antigens and their function in mounting adaptive immune responses. As exosomes provide interesting platforms for antigen presentation, we further review the available data on exosome engineering, which enables peptides of interest to be exposed at their surface. In the light of all these data, exosomes are emerging as promising avenues for vaccine strategies.
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Affiliation(s)
- Daed El Safadi
- Unité Mixte Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de la Réunion, INSERM U1187, CNRS UMR 9192, IRD, Plateforme Technologique CYROI, 94791 Sainte Clotilde, La Réunion, France; (D.E.S.); (A.M.); (G.L.); (W.V.)
| | - Alexandre Mokhtari
- Unité Mixte Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de la Réunion, INSERM U1187, CNRS UMR 9192, IRD, Plateforme Technologique CYROI, 94791 Sainte Clotilde, La Réunion, France; (D.E.S.); (A.M.); (G.L.); (W.V.)
| | - Morgane Krejbich
- Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers, CRCI2NA, INSERM U1307, CNRS UMR 6075, Université de Nantes, Université d’Angers, 8 Quai Moncousu, P.O. Box 70721, Cedex 1, 44007 Nantes, France; (M.K.); (U.H.)
| | - Alisé Lagrave
- Unité Mixte Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de la Réunion, INSERM U1187, CNRS UMR 9192, IRD, Plateforme Technologique CYROI, 94791 Sainte Clotilde, La Réunion, France; (D.E.S.); (A.M.); (G.L.); (W.V.)
- National Reference Center for Arboviruses, Institut Pasteur de la Guyane, Cayenne 97300, French Guiana
| | - Ugo Hirigoyen
- Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes-Angers, CRCI2NA, INSERM U1307, CNRS UMR 6075, Université de Nantes, Université d’Angers, 8 Quai Moncousu, P.O. Box 70721, Cedex 1, 44007 Nantes, France; (M.K.); (U.H.)
| | - Grégorie Lebeau
- Unité Mixte Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de la Réunion, INSERM U1187, CNRS UMR 9192, IRD, Plateforme Technologique CYROI, 94791 Sainte Clotilde, La Réunion, France; (D.E.S.); (A.M.); (G.L.); (W.V.)
- Unité Mixte Diabète Athérothrombose Réunion Océan Indien (DéTROI), Université de La Réunion, INSERM U1188, Campus Santé de Terre Sainte, 97410 Saint-Pierre, La Réunion, France
| | - Wildriss Viranaicken
- Unité Mixte Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de la Réunion, INSERM U1187, CNRS UMR 9192, IRD, Plateforme Technologique CYROI, 94791 Sainte Clotilde, La Réunion, France; (D.E.S.); (A.M.); (G.L.); (W.V.)
- Unité Mixte Diabète Athérothrombose Réunion Océan Indien (DéTROI), Université de La Réunion, INSERM U1188, Campus Santé de Terre Sainte, 97410 Saint-Pierre, La Réunion, France
| | - Pascale Krejbich-Trotot
- Unité Mixte Processus Infectieux en Milieu Insulaire Tropical (PIMIT), Université de la Réunion, INSERM U1187, CNRS UMR 9192, IRD, Plateforme Technologique CYROI, 94791 Sainte Clotilde, La Réunion, France; (D.E.S.); (A.M.); (G.L.); (W.V.)
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25
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Bergin CJ, Zouggar A, Mendes da Silva A, Fenouil T, Haebe JR, Masibag AN, Agrawal G, Shah MS, Sandouka T, Tiberi M, Auer RC, Ardolino M, Benoit YD. The dopamine transporter antagonist vanoxerine inhibits G9a and suppresses cancer stem cell functions in colon tumors. NATURE CANCER 2024; 5:463-480. [PMID: 38351181 DOI: 10.1038/s43018-024-00727-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 01/11/2024] [Indexed: 03/28/2024]
Abstract
Cancer stem cells (CSCs), functionally characterized by self-renewal and tumor-initiating activity, contribute to decreased tumor immunogenicity, while fostering tumor growth and metastasis. Targeting G9a histone methyltransferase (HMTase) effectively blocks CSC functions in colorectal tumors by altering pluripotent-like molecular networks; however, existing molecules directly targeting G9a HMTase activity failed to reach clinical stages due to safety concerns. Using a stem cell-based phenotypic drug-screening pipeline, we identified the dopamine transporter (DAT) antagonist vanoxerine, a compound with previously demonstrated clinical safety, as a cancer-specific downregulator of G9a expression. Here we show that gene silencing and chemical antagonism of DAT impede colorectal CSC functions by repressing G9a expression. Antagonizing DAT also enhanced tumor lymphocytic infiltration by activating endogenous transposable elements and type-I interferon response. Our study unveils the direct implication of the DAT-G9a axis in the maintenance of CSC populations and an approach to improve antitumor immune response in colon tumors.
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Affiliation(s)
- Christopher J Bergin
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Aïcha Zouggar
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Amanda Mendes da Silva
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Tanguy Fenouil
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Inserm U1052, CNRS UMR5286, Centre de Recherche en Cancérologie de Lyon, Université Claude Bernard Lyon 1, Lyon, France
- Institut de Pathologie Multisite des Hospices Civils de Lyon, Site Est, Groupement Hospitalier Est, Bron, France
| | - Joshua R Haebe
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Angelique N Masibag
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Gautam Agrawal
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Muhammad S Shah
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Tamara Sandouka
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Mario Tiberi
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- University of Ottawa Brain and Mind Research Institute, Ottawa, Ontario, Canada
- Neuroscience Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Rebecca C Auer
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Department of Surgery, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Center for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Centre for Infection, Inflammation and Immunity, University of Ottawa, Ottawa, Ontario, Canada
| | - Michele Ardolino
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada
- Center for Cancer Therapeutics, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Centre for Infection, Inflammation and Immunity, University of Ottawa, Ottawa, Ontario, Canada
| | - Yannick D Benoit
- Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
- School of Pharmaceutical Sciences, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
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26
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Madhan S, Dhar R, Devi A. Plant-derived exosomes: a green approach for cancer drug delivery. J Mater Chem B 2024; 12:2236-2252. [PMID: 38351750 DOI: 10.1039/d3tb02752j] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/29/2024]
Abstract
Plant-derived exosomes (PDEs) are natural extracellular vesicles (EVs). In the current decade, they have been highlighted for cancer therapeutic development. Cancer is a global health crisis and it requires an effective, affordable, and less side effect-based treatment. Emerging research based on PDEs suggests that they have immense potential to be considered as a therapeutic option. Research evidences indicate that PDEs' internal molecular cargos show impressive cancer prevention activity with less toxicity. PDEs-based drug delivery systems overcome several limitations of traditional drug delivery tools. Extraction of PDEs from plant sources employ diverse methodologies, encompassing ultracentrifugation, immunoaffinity, size-based isolation, and precipitation, each with distinct advantages and limitations. The core constituents of PDEs comprise of lipids, proteins, DNA, and RNA. Worldwide, a few clinical trials on plant-derived exosomes are underway, and regulatory affairs for their use as therapeutic agents are still not understood with clarity. This review aims to comprehensively analyze the current state of research on plant-derived exosomes as a promising avenue for drug delivery, highlighting anticancer activity, challenges, and future orientation in effective cancer therapeutic development.
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Affiliation(s)
- Shrishti Madhan
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu District - 603 203, Tamil Nadu, India.
| | - Rajib Dhar
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu District - 603 203, Tamil Nadu, India.
| | - Arikketh Devi
- Cancer and Stem Cell Biology Laboratory, Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur, Chengalpattu District - 603 203, Tamil Nadu, India.
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27
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Hashemi A, Ezati M, Nasr MP, Zumberg I, Provaznik V. Extracellular Vesicles and Hydrogels: An Innovative Approach to Tissue Regeneration. ACS OMEGA 2024; 9:6184-6218. [PMID: 38371801 PMCID: PMC10870307 DOI: 10.1021/acsomega.3c08280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/21/2023] [Revised: 11/27/2023] [Accepted: 12/19/2023] [Indexed: 02/20/2024]
Abstract
Extracellular vesicles have emerged as promising tools in regenerative medicine due to their inherent ability to facilitate intercellular communication and modulate cellular functions. These nanosized vesicles transport bioactive molecules, such as proteins, lipids, and nucleic acids, which can affect the behavior of recipient cells and promote tissue regeneration. However, the therapeutic application of these vesicles is frequently constrained by their rapid clearance from the body and inability to maintain a sustained presence at the injury site. In order to overcome these obstacles, hydrogels have been used as extracellular vesicle delivery vehicles, providing a localized and controlled release system that improves their therapeutic efficacy. This Review will examine the role of extracellular vesicle-loaded hydrogels in tissue regeneration, discussing potential applications, current challenges, and future directions. We will investigate the origins, composition, and characterization techniques of extracellular vesicles, focusing on recent advances in exosome profiling and the role of machine learning in this field. In addition, we will investigate the properties of hydrogels that make them ideal extracellular vesicle carriers. Recent studies utilizing this combination for tissue regeneration will be highlighted, providing a comprehensive overview of the current research landscape and potential future directions.
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Affiliation(s)
- Amir Hashemi
- Department
of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3082/12, 61600 Brno, Czech Republic
| | - Masoumeh Ezati
- Department
of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3082/12, 61600 Brno, Czech Republic
| | - Minoo Partovi Nasr
- Department
of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3082/12, 61600 Brno, Czech Republic
| | - Inna Zumberg
- Department
of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3082/12, 61600 Brno, Czech Republic
| | - Valentine Provaznik
- Department
of Biomedical Engineering, Faculty of Electrical Engineering and Communication, Brno University of Technology, Technicka 3082/12, 61600 Brno, Czech Republic
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28
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Cunha E Rocha K, Ying W, Olefsky JM. Exosome-Mediated Impact on Systemic Metabolism. Annu Rev Physiol 2024; 86:225-253. [PMID: 38345906 DOI: 10.1146/annurev-physiol-042222-024535] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/15/2024]
Abstract
Exosomes are small extracellular vesicles that carry lipids, proteins, and microRNAs (miRNAs). They are released by all cell types and can be found not only in circulation but in many biological fluids. Exosomes are essential for interorgan communication because they can transfer their contents from donor to recipient cells, modulating cellular functions. The miRNA content of exosomes is responsible for most of their biological effects, and changes in exosomal miRNA levels can contribute to the progression or regression of metabolic diseases. As exosomal miRNAs are selectively sorted and packaged into exosomes, they can be useful as biomarkers for diagnosing diseases. The field of exosomes and metabolism is expanding rapidly, and researchers are consistently making new discoveries in this area. As a result, exosomes have great potential for a next-generation drug delivery platform for metabolic diseases.
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Affiliation(s)
- Karina Cunha E Rocha
- Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California, USA;
| | - Wei Ying
- Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California, USA;
| | - Jerrold M Olefsky
- Department of Medicine, Division of Endocrinology and Metabolism, University of California, San Diego, La Jolla, California, USA;
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29
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Fang F, Yang J, Wang J, Li T, Wang E, Zhang D, Liu X, Zhou C. The role and applications of extracellular vesicles in osteoporosis. Bone Res 2024; 12:4. [PMID: 38263267 PMCID: PMC10806231 DOI: 10.1038/s41413-023-00313-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2023] [Revised: 11/13/2023] [Accepted: 11/28/2023] [Indexed: 01/25/2024] Open
Abstract
Osteoporosis is a widely observed condition characterized by the systemic deterioration of bone mass and microarchitecture, which increases patient susceptibility to fragile fractures. The intricate mechanisms governing bone homeostasis are substantially impacted by extracellular vesicles (EVs), which play crucial roles in both pathological and physiological contexts. EVs derived from various sources exert distinct effects on osteoporosis. Specifically, EVs released by osteoblasts, endothelial cells, myocytes, and mesenchymal stem cells contribute to bone formation due to their unique cargo of proteins, miRNAs, and cytokines. Conversely, EVs secreted by osteoclasts and immune cells promote bone resorption and inhibit bone formation. Furthermore, the use of EVs as therapeutic modalities or biomaterials for diagnosing and managing osteoporosis is promising. Here, we review the current understanding of the impact of EVs on bone homeostasis, including the classification and biogenesis of EVs and the intricate regulatory mechanisms of EVs in osteoporosis. Furthermore, we present an overview of the latest research progress on diagnosing and treating osteoporosis by using EVs. Finally, we discuss the challenges and prospects of translational research on the use of EVs in osteoporosis.
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Affiliation(s)
- Fei Fang
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China
| | - Jie Yang
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China
| | - Jiahe Wang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Tiantian Li
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China
| | - Erxiang Wang
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China
| | - Demao Zhang
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Xiaoheng Liu
- Institute of Biomedical Engineering, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, 610041, China.
| | - Chenchen Zhou
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
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30
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Yang J, Zhang Z, Lam JSW, Fan H, Fu NY. Molecular Regulation and Oncogenic Functions of TSPAN8. Cells 2024; 13:193. [PMID: 38275818 PMCID: PMC10814125 DOI: 10.3390/cells13020193] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2024] [Revised: 01/17/2024] [Accepted: 01/18/2024] [Indexed: 01/27/2024] Open
Abstract
Tetraspanins, a superfamily of small integral membrane proteins, are characterized by four transmembrane domains and conserved protein motifs that are configured into a unique molecular topology and structure in the plasma membrane. They act as key organizers of the plasma membrane, orchestrating the formation of specialized microdomains called "tetraspanin-enriched microdomains (TEMs)" or "tetraspanin nanodomains" that are essential for mediating diverse biological processes. TSPAN8 is one of the earliest identified tetraspanin members. It is known to interact with a wide range of molecular partners in different cellular contexts and regulate diverse molecular and cellular events at the plasma membrane, including cell adhesion, migration, invasion, signal transduction, and exosome biogenesis. The functions of cell-surface TSPAN8 are governed by ER targeting, modifications at the Golgi apparatus and dynamic trafficking. Intriguingly, limited evidence shows that TSPAN8 can translocate to the nucleus to act as a transcriptional regulator. The transcription of TSPAN8 is tightly regulated and restricted to defined cell lineages, where it can serve as a molecular marker of stem/progenitor cells in certain normal tissues as well as tumors. Importantly, the oncogenic roles of TSPAN8 in tumor development and cancer metastasis have gained prominence in recent decades. Here, we comprehensively review the current knowledge on the molecular characteristics and regulatory mechanisms defining TSPAN8 functions, and discuss the potential and significance of TSPAN8 as a biomarker and therapeutic target across various epithelial cancers.
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Affiliation(s)
- Jicheng Yang
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, Singapore
- ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medicine, University of Melbourne, Parkville, VIC 3010, Australia
| | - Ziyan Zhang
- ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medicine, University of Melbourne, Parkville, VIC 3010, Australia
| | - Joanne Shi Woon Lam
- Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore 138671, Singapore
| | - Hao Fan
- Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR), Singapore 138671, Singapore
| | - Nai Yang Fu
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore 169857, Singapore
- ACRF Cancer Biology and Stem Cells Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia
- Department of Medicine, University of Melbourne, Parkville, VIC 3010, Australia
- Department of Physiology, National University of Singapore, Singapore 117593, Singapore
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31
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Wang W, Wu X, Zheng J, Yin R, Li Y, Wu X, Xu L, Jin Z. Utilizing exosomes as sparking clinical biomarkers and therapeutic response in acute myeloid leukemia. Front Immunol 2024; 14:1315453. [PMID: 38292478 PMCID: PMC10824954 DOI: 10.3389/fimmu.2023.1315453] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2023] [Accepted: 12/29/2023] [Indexed: 02/01/2024] Open
Abstract
Acute myeloid leukemia (AML) is a malignant clonal tumor originating from immature myeloid hematopoietic cells in the bone marrow with rapid progression and poor prognosis. Therefore, an in-depth exploration of the pathogenesis of AML can provide new ideas for the treatment of AML. In recent years, it has been found that exosomes play an important role in the pathogenesis of AML. Exosomes are membrane-bound extracellular vesicles (EVs) that transfer signaling molecules and have attracted a large amount of attention, which are key mediators of intercellular communication. Extracellular vesicles not only affect AML cells and normal hematopoietic cells but also have an impact on the bone marrow microenvironment and immune escape, thereby promoting the progression of AML and leading to refractory relapse. It is worth noting that exosomes and the various molecules they contain are expected to become the new markers for disease monitoring and prognosis of AML, and may also function as drug carriers and vaccines to enhance the treatment of leukemia. In this review, we mainly summarize to reveal the role of exosomes in AML pathogenesis, which helps us elucidate the application of exosomes in AML diagnosis and treatment.
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Affiliation(s)
- Wandi Wang
- Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
| | - Xiaofang Wu
- Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
| | - Jiamian Zheng
- Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
| | - Ran Yin
- Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
| | - Yangqiu Li
- Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
| | - Xiuli Wu
- Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
- Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China
| | - Ling Xu
- Institute of Hematology, School of Medicine, Jinan University, Guangzhou, China
- Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China
| | - Zhenyi Jin
- Department of Pathology, School of Medicine, Jinan University, Guangzhou, China
- Key Laboratory of Viral Pathogenesis and Infection Prevention and Control, Jinan University, Guangzhou, China
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32
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Akbari-Gharalari N, Khodakarimi S, Nezhadshahmohammad F, Karimipour M, Ebrahimi-Kalan A, Wu J. Exosomes in neuron-glia communication: A review on neurodegeneration. BIOIMPACTS : BI 2024; 14:30153. [PMID: 39296798 PMCID: PMC11406431 DOI: 10.34172/bi.2023.30153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 12/03/2023] [Accepted: 01/02/2024] [Indexed: 09/21/2024]
Abstract
Introduction Exosomes, a subset of extracellular vesicles (EVs), are crucial for intercellular communication in various contexts. Despite their small size, they carry diverse cargo, including RNA, proteins, and lipids. Internalization by recipient cells raises concerns about potential disruptions to cellular functions. Notably, the ability of exosomes to traverse the blood-brain barrier (BBB) has significant implications. Methods To conduct a thorough investigation into the existing academic literature on exosomes within the framework of neuron-glia communication, a comprehensive search strategy was implemented across the PubMed, Google Scholar, and Science Direct databases. Multiple iterations of the keywords "exosome," "neuron-glia communication," and "neurological disorders" were employed to systematically identify relevant publications. Furthermore, an exploration of the Clinicaltrials.gov database was undertaken to identify clinical trials related to cellular signaling, utilizing analogous terminology. Results Although the immediate practical applications of exosomes are somewhat limited, their potential as carriers of pathogenic attributes offers promising opportunities for the development of precisely targeted therapeutic strategies for neurological disorders. This review presents a comprehensive overview of contemporary insights into the pivotal roles played by exosomes as agents mediating communication between neurons and glial cells within the central nervous system (CNS). Conclusion By delving into the intricate dynamics of exosomal communication in the CNS, this review contributes to a deeper understanding of the roles of exosomes in both physiological and pathological processes, thereby paving the way for potential therapeutic advancements in the field of neurological disorders.
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Affiliation(s)
- Naeimeh Akbari-Gharalari
- Department of Neurosciences and Cognition, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Sina Khodakarimi
- Department of Neurosciences and Cognition, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Mohammad Karimipour
- Department of Anatomical Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Abbas Ebrahimi-Kalan
- Department of Neurosciences and Cognition, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Jiagian Wu
- The Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
- Center for Stem Cell and Regenerative Medicine, UT Brown Foundation Institute of Molecular Medicine, Houston, TX 77030, USA
- MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
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33
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Yu J, Sane S, Kim JE, Yun S, Kim HJ, Jo KB, Wright JP, Khoshdoozmasouleh N, Lee K, Oh HT, Thiel K, Parvin A, Williams X, Hannon C, Lee H, Kim DK. Biogenesis and delivery of extracellular vesicles: harnessing the power of EVs for diagnostics and therapeutics. Front Mol Biosci 2024; 10:1330400. [PMID: 38234582 PMCID: PMC10791869 DOI: 10.3389/fmolb.2023.1330400] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Accepted: 11/28/2023] [Indexed: 01/19/2024] Open
Abstract
Extracellular vesicles (EVs) are membrane-enclosed particles secreted by a variety of cell types. These vesicles encapsulate a diverse range of molecules, including proteins, nucleic acids, lipids, metabolites, and even organelles derived from their parental cells. While EVs have emerged as crucial mediators of intercellular communication, they also hold immense potential as both biomarkers and therapeutic agents for numerous diseases. A thorough understanding of EV biogenesis is crucial for the development of EV-based diagnostic developments since the composition of EVs can reflect the health and disease status of the donor cell. Moreover, when EVs are taken up by target cells, they can exert profound effects on gene expression, signaling pathways, and cellular behavior, which makes these biomolecules enticing targets for therapeutic interventions. Yet, despite decades of research, the intricate processes underlying EV biogenesis by donor cells and subsequent uptake by recipient cells remain poorly understood. In this review, we aim to summarize current insights and advancements in the biogenesis and uptake mechanisms of EVs. By shedding light on the fundamental mechanisms governing EV biogenesis and delivery, this review underscores the potential of basic mechanistic research to pave the way for developing novel diagnostic strategies and therapeutic applications.
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Affiliation(s)
- Jivin Yu
- Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Saba Sane
- Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Ji-Eun Kim
- Department of Experimental Animal Research, Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea
| | - Sehee Yun
- Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Hyeon-Jai Kim
- Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Kyeong Beom Jo
- Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Jacob P. Wright
- Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
- College of Arts and Sciences, University at Buffalo, Buffalo, NY, United States
| | - Nooshin Khoshdoozmasouleh
- Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Kunwoo Lee
- Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Ho Taek Oh
- Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Keaton Thiel
- Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Afrin Parvin
- Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Xavier Williams
- Applied Technology Laboratory for Advanced Surgery (ATLAS) Studios Resource, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Claire Hannon
- Applied Technology Laboratory for Advanced Surgery (ATLAS) Studios Resource, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
| | - Hunsang Lee
- Department of Life Sciences, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
| | - Dae-Kyum Kim
- Department of Cancer Genetics and Genomics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, United States
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Reseco L, Molina-Crespo A, Atienza M, Gonzalez E, Falcon-Perez JM, Cantero JL. Characterization of Extracellular Vesicles from Human Saliva: Effects of Age and Isolation Techniques. Cells 2024; 13:95. [PMID: 38201299 PMCID: PMC10778510 DOI: 10.3390/cells13010095] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 12/22/2023] [Accepted: 12/22/2023] [Indexed: 01/12/2024] Open
Abstract
Salivary extracellular vesicles (EVs) represent an attractive source of biomarkers due to the accessibility of saliva and its non-invasive sampling methods. However, the lack of comparative studies assessing the efficacy of different EV isolation techniques hampers the use of salivary EVs in clinical settings. Moreover, the effects of age on salivary EVs are largely unknown, hindering the identification of salivary EV-associated biomarkers across the lifespan. To address these questions, we compared salivary EV concentration, size mode, protein concentration, and purity using eight EV isolation techniques before and after magnetic bead immunocapture with antibodies against CD9, CD63, and CD81. The effects of age on salivary EVs obtained with each isolation technique were further investigated. Results showed higher expression of CD63 on isolated salivary EVs compared to the expression of CD81 and flotillin-1. Overall, magnetic bead immunocapture was more efficient in recovering salivary EVs with Norgen's Saliva Exosome Purification Kit and ExoQuick-TC ULTRA at the cost of EV yield. Regardless of age, Invitrogen Total Exosome Isolation Solution showed the highest level of protein concentration, whereas Izon qEVOriginal-70nm columns revealed the highest purity. This study provides the first comprehensive comparison of salivary EVs in younger and older adults using different EV isolation techniques, which represents a step forward for assessing salivary EVs as a source of potential biomarkers of tissue-specific diseases throughout the life cycle.
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Affiliation(s)
- Lucia Reseco
- Laboratory of Functional Neuroscience, Pablo de Olavide University, 41013 Seville, Spain; (L.R.); (A.M.-C.); (M.A.)
- CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Angela Molina-Crespo
- Laboratory of Functional Neuroscience, Pablo de Olavide University, 41013 Seville, Spain; (L.R.); (A.M.-C.); (M.A.)
- CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Mercedes Atienza
- Laboratory of Functional Neuroscience, Pablo de Olavide University, 41013 Seville, Spain; (L.R.); (A.M.-C.); (M.A.)
- CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Esperanza Gonzalez
- Exosomes Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), 48160 Derio, Spain; (E.G.); (J.M.F.-P.)
| | - Juan Manuel Falcon-Perez
- Exosomes Laboratory, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), 48160 Derio, Spain; (E.G.); (J.M.F.-P.)
- CIBEREHD, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, 28029 Madrid, Spain
| | - Jose L. Cantero
- Laboratory of Functional Neuroscience, Pablo de Olavide University, 41013 Seville, Spain; (L.R.); (A.M.-C.); (M.A.)
- CIBERNED, Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Instituto de Salud Carlos III, 28029 Madrid, Spain
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Nelson H, Qu S, Franklin JL, Liu Q, Pua HH, Vickers KC, Weaver AM, Coffey RJ, Patton JG. Extracellular RNA in oncogenesis, metastasis and drug resistance. RNA Biol 2024; 21:17-31. [PMID: 39107918 PMCID: PMC11639457 DOI: 10.1080/15476286.2024.2385607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 07/09/2024] [Accepted: 07/24/2024] [Indexed: 08/18/2024] Open
Abstract
Extracellular vesicles and nanoparticles (EVPs) are now recognized as a novel form of cell-cell communication. All cells release a wide array of heterogeneous EVPs with distinct protein, lipid, and RNA content, dependent on the pathophysiological state of the donor cell. The overall cargo content in EVPs is not equivalent to cellular levels, implying a regulated pathway for selection and export. In cancer, release and uptake of EVPs within the tumour microenvironment can influence growth, proliferation, invasiveness, and immune evasion. Secreted EVPs can also have distant, systemic effects that can promote metastasis. Here, we review current knowledge of EVP biogenesis and cargo selection with a focus on the role that extracellular RNA plays in oncogenesis and metastasis. Almost all subtypes of RNA have been identified in EVPs, with miRNAs being the best characterized. We review the roles of specific miRNAs that have been detected in EVPs and that play a role in oncogenesis and metastasis.
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Affiliation(s)
- Hannah Nelson
- Department of Biological Sciences, Vanderbilt University and Vanderbilt University Medical Center, Nashville, TN, USA
- Center for Extracellular Vesicle Research, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Sherman Qu
- Department of Biological Sciences, Vanderbilt University and Vanderbilt University Medical Center, Nashville, TN, USA
- Center for Extracellular Vesicle Research, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Jeffrey L. Franklin
- Center for Extracellular Vesicle Research, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Qi Liu
- Center for Extracellular Vesicle Research, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Biostatistics, Vanderbilt University and Vanderbilt University Medical Center, Nashville, TN, USA
| | - Heather H. Pua
- Center for Extracellular Vesicle Research, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University and Vanderbilt University Medical Center, Nashville, TN, USA
| | - Kasey C. Vickers
- Center for Extracellular Vesicle Research, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Medicine, Vanderbilt University and Vanderbilt University Medical Center, Nashville, TN, USA
| | - Alissa M. Weaver
- Center for Extracellular Vesicle Research, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA
| | - Robert J. Coffey
- Center for Extracellular Vesicle Research, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA
- Department of Medicine, Vanderbilt University and Vanderbilt University Medical Center, Nashville, TN, USA
| | - James G. Patton
- Department of Biological Sciences, Vanderbilt University and Vanderbilt University Medical Center, Nashville, TN, USA
- Center for Extracellular Vesicle Research, Vanderbilt University School of Medicine, Nashville, TN, USA
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Singh S, Dansby C, Agarwal D, Bhat PD, Dubey PK, Krishnamurthy P. Exosomes: Methods for Isolation and Characterization in Biological Samples. Methods Mol Biol 2024; 2835:181-213. [PMID: 39105917 DOI: 10.1007/978-1-0716-3995-5_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/07/2024]
Abstract
Exosomes are small lipid bilayer-encapsulated nanosized extracellular vesicles of endosomal origin. Exosomes are secreted by almost all cell types and are a crucial player in intercellular communication. Exosomes transmit cellular information from donor to recipient cells in the form of proteins, lipids, and nucleic acids and influence several physiological and pathological responses. Due to their capacity to carry a variety of cellular cargo, low immunogenicity and cytotoxicity, biocompatibility, and ability to cross the blood-brain barrier, these nanosized vesicles are considered excellent diagnostic tools and drug-delivery vehicles. Despite their tremendous potential, the progress in therapeutic applications of exosomes is hindered by inadequate isolation techniques, poor characterization, and scarcity of specific biomarkers. The current research in the field is focused on overcoming these limitations. In this chapter, we have reviewed conventional exosome isolation and characterization methods and recent advancements, their advantages and limitations, persistent challenges in exosome research, and future directions.
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Affiliation(s)
- Sarojini Singh
- Department of Biomedical Engineering, Heersink School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Cassidy Dansby
- Department of Biomedical Engineering, Heersink School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Divyanshi Agarwal
- Department of Biomedical Engineering, Heersink School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Purnima Devaki Bhat
- Department of Biomedical Engineering, Heersink School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Praveen Kumar Dubey
- Department of Biomedical Engineering, Heersink School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Prasanna Krishnamurthy
- Department of Biomedical Engineering, Heersink School of Medicine and School of Engineering, University of Alabama at Birmingham, Birmingham, AL, USA.
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Potrich C, Pedrotti A, Pederzolli C, Lunelli L. Functional surfaces for exosomes capturing and exosomal microRNAs analysis. Colloids Surf B Biointerfaces 2024; 233:113627. [PMID: 37948834 DOI: 10.1016/j.colsurfb.2023.113627] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Revised: 10/19/2023] [Accepted: 10/26/2023] [Indexed: 11/12/2023]
Abstract
Exosomes are small extracellular vesicles well-studied both as cell signaling elements and as source of highly informative biomarkers, in particular microRNAs. Standard techniques for exosome isolation are in general scarcely efficient and give low purity vesicles. New techniques combining microfluidics with suitable functionalized surfaces could overcome these disadvantages. Here, different functional surfaces aimed at exosomes capture are developed thank to the functionalization of silicon oxide substrates. Charged surfaces, both positive and negative, neutral and immunoaffinity surfaces are characterized and tested in functional assays with both exosome mimicking vesicles and exosomes purified from cell supernatants. The different surfaces showed promising properties, in particular the negatively-charged surface could capture more than 4 × 108 exosomes per square centimeter. The captured exosomes could be recovered and their biomarker cargo analyzed. Exosomal microRNAs were successfully analyzed with RT-PCR, confirming the good performances of the negatively-charged surface. The best-performing functionalization could be easily moved to microdevice surfaces for developing modular microfluidic systems for on-chip isolation of exosomes, to be integrated in simple and fast biosensors aimed at biomarker analysis both in clinical settings and in research.
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Affiliation(s)
- Cristina Potrich
- FBK-Fondazione Bruno Kessler, Center for Sensors and Devices, via Sommarive, 18, I-38123, Trento, Italy; Consiglio Nazionale delle Ricerche, Istituto di Biofisica, via alla Cascata 56/C, I-38123, Trento, Italy.
| | - Anna Pedrotti
- FBK-Fondazione Bruno Kessler, Center for Sensors and Devices, via Sommarive, 18, I-38123, Trento, Italy
| | - Cecilia Pederzolli
- FBK-Fondazione Bruno Kessler, Center for Sensors and Devices, via Sommarive, 18, I-38123, Trento, Italy
| | - Lorenzo Lunelli
- FBK-Fondazione Bruno Kessler, Center for Sensors and Devices, via Sommarive, 18, I-38123, Trento, Italy; Consiglio Nazionale delle Ricerche, Istituto di Biofisica, via alla Cascata 56/C, I-38123, Trento, Italy
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Fontelonga T, Hall AJ, Brown JL, Jung YL, Alexander MS, Dominov JA, Mouly V, Vieira N, Zatz M, Vainzof M, Gussoni E. Tetraspanin CD82 Associates with Trafficking Vesicle in Muscle Cells and Binds to Dysferlin and Myoferlin. Adv Biol (Weinh) 2023; 7:e2300157. [PMID: 37434585 PMCID: PMC10784410 DOI: 10.1002/adbi.202300157] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Revised: 06/26/2023] [Indexed: 07/13/2023]
Abstract
Tetraspanins organize protein complexes at the cell membrane and are responsible for assembling diverse binding partners in changing cellular states. Tetraspanin CD82 is a useful cell surface marker for prospective isolation of human myogenic progenitors and its expression is decreased in Duchenne muscular dystrophy (DMD) cell lines. The function of CD82 in skeletal muscle remains elusive, partly because the binding partners of this tetraspanin in muscle cells have not been identified. CD82-associated proteins are sought to be identified in human myotubes via mass spectrometry proteomics, which identifies dysferlin and myoferlin as CD82-binding partners. In human dysferlinopathy (Limb girdle muscular dystrophy R2, LGMDR2) myogenic cell lines, expression of CD82 protein is near absent in two of four patient samples. In the cell lines where CD82 protein levels are unaffected, increased expression of the ≈72 kDa mini-dysferlin product is identified using an antibody recognizing the dysferlin C-terminus. These data demonstrate that CD82 binds dysferlin/myoferlin in differentiating muscle cells and its expression can be affected by loss of dysferlin in human myogenic cells.
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Affiliation(s)
| | - Arielle J. Hall
- Division of Genetics and Genomics, Boston Children’s Hospital, MA, USA
| | - Jaedon L. Brown
- Division of Genetics and Genomics, Boston Children’s Hospital, MA, USA
| | - Youngsook L. Jung
- Division of Genetics and Genomics, Boston Children’s Hospital, MA, USA
| | - Matthew S. Alexander
- Department of Pediatrics, Division of Neurology at Children’s of Alabama, University of Alabama at Birmingham, Birmingham, AL, USA
- Department of Genetics, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Janice A. Dominov
- Department of Neurology, University of Massachusetts Worcester, MA, USA
| | | | | | - Mayana Zatz
- Human Genome and Stem Cells Research Center, Biosciences Institute, University of São Paulo, São Paulo, BR
| | - Mariz Vainzof
- Human Genome and Stem Cells Research Center, Biosciences Institute, University of São Paulo, São Paulo, BR
| | - Emanuela Gussoni
- Division of Genetics and Genomics, Boston Children’s Hospital, MA, USA
- The Stem Cell Program, Boston Children’s Hospital, Boston, MA, USA
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Monsalve RI, Lombardero M, Christensen LH, Núñez-Acevedo B, González-de-Olano D, Sobrino-García M, Castillo-Loja RM, Bravo SB, Alonso-Sampedro M, Vidal C. Structural Similarities, in Relation with the Cross-Reactivity, of Hymenoptera Allergenic Dipeptidyl Peptidases IV-An Overall Comparison Including a New Dipeptidyl Peptidase IV Sequence from Vespa velutina. Toxins (Basel) 2023; 15:656. [PMID: 37999519 PMCID: PMC10675595 DOI: 10.3390/toxins15110656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 10/31/2023] [Accepted: 11/08/2023] [Indexed: 11/25/2023] Open
Abstract
(1) Background: Dipeptidyl Peptidases IV (DPPIVs), present in many organisms, are minor components in the venoms of Hymenoptera, where they have been identified as cross-reactive allergenic molecules. Considering that the structure of homologous DPPIVs is well characterized, we aimed to explain which regions have higher similarity among these proteins and present a comparison among them, including a new Vespa velutina DPPIV sequence. Moreover, two cases of sensitization to DPPIVs in wasp- and honeybee-sensitized patients are presented. (2) Methods: Proteomic analyses have been performed on the venom of the Asian hornet Vespa velutina to demonstrate the sequence of its DPPIV (allergen named Vesp v 3, with sequence accession number P0DRB8, and with the proteomic data available via ProteomeXchange with the identifier PXD046030). A comparison performed through their alignments and analysis of the three-dimensional structure showed a region with higher similarity among Hymenoptera DPPIVs. Additionally, ImmunoCAP™ determinations (including specific inhibition experiments), as well as IgE immunoblotting, are performed to demonstrate the allergenicity of Api m 5 and Ves v 3. (3) Results and Conclusions: The data presented demonstrate that the similarities among Hymenoptera DPPIVs are most likely localized at the C-terminal region of these enzymes. In addition, a higher similarity of the Vespa/Vespula DPPIVs is shown. The clinical cases analyzed demonstrated the allergenicity of Api m 5 and Ves v 3 in the sera of the allergic patients, as well as the presence of this minor component in the preparations used in venom immunotherapy.
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Affiliation(s)
| | | | | | - Beatriz Núñez-Acevedo
- Allergology Service, Hospital Universitario Infanta Sofía, San Sebastián de los Reyes, 28702 Madrid, Spain;
| | - David González-de-Olano
- Allergy Service, Hospital Ramón y Cajal, IRYCIS (Instituto Ramón y Cajal de Investigación Sanitaria), 28034 Madrid, Spain;
| | | | - Rosita M. Castillo-Loja
- Biosanitary Institute, IBSAL (Instituto de Investigación Biomédica de Salamanca), 37007 Salamanca, Spain;
| | - Susana B. Bravo
- Proteomic Unit, Health Research Institute of Santiago de Compostela (IDIS), University Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain;
| | - Manuela Alonso-Sampedro
- Research Methods Group (RESMET), Health Research Institute of Santiago de Compostela (IDIS), Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS-ISCIII/RD21/0016/0022), University Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain;
| | - Carmen Vidal
- Research Methods Group (RESMET), Health Research Institute of Santiago de Compostela (IDIS), Network for Research on Chronicity, Primary Care, and Health Promotion (RICAPPS-ISCIII/RD21/0016/0022), University Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain;
- Allergy Department, University Hospital of Santiago de Compostela, 15706 Santiago de Compostela, Spain;
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Shibata C, Otsuka M, Shimizu T, Seimiya T, Kishikawa T, Aoki T, Fujishiro M. Extracellular vesicle‑mediated RNA editing may underlie the heterogeneity and spread of hepatocellular carcinoma in human tissue and in vitro. Oncol Rep 2023; 50:194. [PMID: 37732519 PMCID: PMC10539718 DOI: 10.3892/or.2023.8631] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 08/01/2023] [Indexed: 09/22/2023] Open
Abstract
Extracellular vesicles (EVs) produced by various cells, including tumor cells, carry biomolecules to neighboring cells. In hepatocellular carcinoma (HCC), adenosine to inosine RNA editing of antizyme inhibitor 1 (AZIN1), specifically regulated by adenosine deaminase acting on RNA‑1 (ADAR1), promotes carcinogenesis. The present study examined if EVs and ADAR1 in the EVs released from HCC cells are transferred to neighboring cells in co‑culture systems and reporter assay. Distribution of the ADAR1 expression in human tissues were examined by immunohistochemistry. EVs released from HCC cells containing ADAR1 were delivered to neighboring HCC cells and non‑cancerous hepatocytes. The increased ADAR1 protein levels resulted in serine to glycine substitution at residue 367 of AZIN1, which augmented transformation potential and increased aggressive behavior of cancer cells. In clinically resected samples, ADAR1 distribution was highly heterogeneous within the tumor specimen and denser in non‑cancerous tissue surrounding the HCC tissue. These observations suggested that ADAR1 protein may be delivered from HCC cells to neighboring cells via EVs and that EV‑mediated RNA editing may serve a pivotal role in determining HCC heterogeneity and spread.
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Affiliation(s)
- Chikako Shibata
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
- Research Fellow of Japan Society for the Promotion of Science, Tokyo 102-0083, Japan
| | - Motoyuki Otsuka
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Density and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan
| | - Takayuki Shimizu
- Department of Hepatobiliary and Pancreatic Surgery, Dokkyo Medical University, Tochigi 321-0293, Japan
| | - Takahiro Seimiya
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Takahiro Kishikawa
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
| | - Taku Aoki
- Department of Hepatobiliary and Pancreatic Surgery, Dokkyo Medical University, Tochigi 321-0293, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, Japan
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Osaid Z, Haider M, Hamoudi R, Harati R. Exosomes Interactions with the Blood-Brain Barrier: Implications for Cerebral Disorders and Therapeutics. Int J Mol Sci 2023; 24:15635. [PMID: 37958619 PMCID: PMC10648512 DOI: 10.3390/ijms242115635] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 10/23/2023] [Accepted: 10/24/2023] [Indexed: 11/15/2023] Open
Abstract
The Blood-Brain Barrier (BBB) is a selective structural and functional barrier between the circulatory system and the cerebral environment, playing an essential role in maintaining cerebral homeostasis by limiting the passage of harmful molecules. Exosomes, nanovesicles secreted by virtually all cell types into body fluids, have emerged as a major mediator of intercellular communication. Notably, these vesicles can cross the BBB and regulate its physiological functions. However, the precise molecular mechanisms by which exosomes regulate the BBB remain unclear. Recent research studies focused on the effect of exosomes on the BBB, particularly in the context of their involvement in the onset and progression of various cerebral disorders, including solid and metastatic brain tumors, stroke, neurodegenerative, and neuroinflammatory diseases. This review focuses on discussing and summarizing the current knowledge about the role of exosomes in the physiological and pathological modulation of the BBB. A better understanding of this regulation will improve our understanding of the pathogenesis of cerebral diseases and will enable the design of effective treatment strategies.
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Affiliation(s)
- Zaynab Osaid
- Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates;
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates;
| | - Mohamed Haider
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates;
- Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates
| | - Rifat Hamoudi
- Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates;
- Division of Surgery and Interventional Science, University College London, London W1W 7EJ, UK
| | - Rania Harati
- Department of Pharmacy Practice and Pharmacotherapeutics, College of Pharmacy, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates;
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah P.O. Box 27272, United Arab Emirates;
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Wandrey M, Jablonska J, Stauber RH, Gül D. Exosomes in Cancer Progression and Therapy Resistance: Molecular Insights and Therapeutic Opportunities. Life (Basel) 2023; 13:2033. [PMID: 37895415 PMCID: PMC10608050 DOI: 10.3390/life13102033] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 10/04/2023] [Accepted: 10/05/2023] [Indexed: 10/29/2023] Open
Abstract
The development of therapy resistance still represents a major hurdle in treating cancers, leading to impaired treatment success and increased patient morbidity. The establishment of minimally invasive liquid biopsies is a promising approach to improving the early diagnosis, as well as therapy monitoring, of solid tumors. Because of their manifold functions in the tumor microenvironment, tumor-associated small extracellular vesicles, referred to as exosomes, have become a subject of intense research. Besides their important roles in cancer progression, metastasis, and the immune response, it has been proposed that exosomes also contribute to the acquisition and transfer of therapy resistance, mainly by delivering functional proteins and RNAs, as well as facilitating the export of active drugs or functioning as extracellular decoys. Extensive research has focused on understanding the molecular mechanisms underlying the occurrence of resistance and translating these into strategies for early detection. With this review, we want to provide an overview of the current knowledge about the (patho-)biology of exosomes, as well as state-of-the-art methods of isolation and analysis. Furthermore, we highlight the role of exosomes in tumorigenesis and cancer treatment, where they can function as therapeutic agents, biomarkers, and/or targets. By focusing on their roles in therapy resistance, we will reveal new paths of exploiting exosomes for cancer diagnosis and treatment.
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Affiliation(s)
- Madita Wandrey
- Nanobiomedicine/ENT Department, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany; (M.W.); (R.H.S.)
| | - Jadwiga Jablonska
- Translational Oncology/ENT Department, University Hospital Essen, Hufelandstraße 55, 45147 Essen, Germany;
- German Cancer Consortium (DKTK) Partner Site Düsseldorf/Essen, 45147 Essen, Germany
| | - Roland H. Stauber
- Nanobiomedicine/ENT Department, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany; (M.W.); (R.H.S.)
| | - Désirée Gül
- Nanobiomedicine/ENT Department, University Medical Center Mainz, Langenbeckstraße 1, 55131 Mainz, Germany; (M.W.); (R.H.S.)
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Islam MK, Khan M, Gidwani K, Witwer KW, Lamminmäki U, Leivo J. Lectins as potential tools for cancer biomarker discovery from extracellular vesicles. Biomark Res 2023; 11:85. [PMID: 37773167 PMCID: PMC10540341 DOI: 10.1186/s40364-023-00520-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Accepted: 09/01/2023] [Indexed: 10/01/2023] Open
Abstract
Extracellular vesicles (EVs) have considerable potential as diagnostic, prognostic, and therapeutic agents, in large part because molecular patterns on the EV surface betray the cell of origin and may also be used to "target" EVs to specific cells. Cancer is associated with alterations to cellular and EV glycosylation patterns, and the surface of EVs is enriched with glycan moieties. Glycoconjugates of EVs play versatile roles in cancer including modulating immune response, affecting tumor cell behavior and site of metastasis and as such, paving the way for the development of innovative diagnostic tools and novel therapies. Entities that recognize specific glycans, such as lectins, may thus be powerful tools to discover and detect novel cancer biomarkers. Indeed, the past decade has seen a constant increase in the number of published articles on lectin-based strategies for the detection of EV glycans. This review explores the roles of EV glycosylation in cancer and cancer-related applications. Furthermore, this review summarizes the potential of lectins and lectin-based methods for screening, targeting, separation, and possible identification of improved biomarkers from the surface of EVs.
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Affiliation(s)
- Md Khirul Islam
- Department of Life Technologies, Division of Biotechnology, University of Turku, Kiinamyllynkatu 10, 20014, Turku, Finland.
- InFLAMES Research Flagship Center, University of Turku, Turku, Finland.
| | - Misba Khan
- Department of Life Technologies, Division of Biotechnology, University of Turku, Kiinamyllynkatu 10, 20014, Turku, Finland
| | - Kamlesh Gidwani
- Department of Life Technologies, Division of Biotechnology, University of Turku, Kiinamyllynkatu 10, 20014, Turku, Finland
| | - Kenneth W Witwer
- Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
- Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - Urpo Lamminmäki
- Department of Life Technologies, Division of Biotechnology, University of Turku, Kiinamyllynkatu 10, 20014, Turku, Finland
- InFLAMES Research Flagship Center, University of Turku, Turku, Finland
| | - Janne Leivo
- Department of Life Technologies, Division of Biotechnology, University of Turku, Kiinamyllynkatu 10, 20014, Turku, Finland
- InFLAMES Research Flagship Center, University of Turku, Turku, Finland
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Liu Q, Li D, Pan X, Liang Y. Targeted therapy using engineered extracellular vesicles: principles and strategies for membrane modification. J Nanobiotechnology 2023; 21:334. [PMID: 37717008 PMCID: PMC10505332 DOI: 10.1186/s12951-023-02081-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2023] [Accepted: 08/26/2023] [Indexed: 09/18/2023] Open
Abstract
Extracellular vesicles (EVs) are 30-150 nm membrane-bound vesicles naturally secreted by cells and play important roles in intercellular communication by delivering regulatory molecules such as proteins, lipids, nucleic acids and metabolites to recipient cells. As natural nano-carriers, EVs possess desirable properties such as high biocompatibility, biological barrier permeability, low toxicity, and low immunogenicity, making them potential therapeutic delivery vehicles. EVs derived from specific cells have inherent targeting capacity towards specific cell types, which is yet not satisfactory enough for targeted therapy development and needs to be improved. Surface modifications endow EVs with targeting abilities, significantly improving their therapeutic efficiency. Herein, we first briefly introduce the biogenesis, composition, uptake and function of EVs, and review the cargo loading approaches for EVs. Then, we summarize the recent advances in surface engineering strategies of EVs, focusing on the applications of engineered EVs for targeted therapy. Altogether, EVs hold great promise for targeted delivery of various cargos, and targeted modifications show promising effects on multiple diseases.
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Affiliation(s)
- Qisong Liu
- National Clinical Research Center for Infectious Diseases, Shenzhen Third People's Hospital, Southern University of Science and Technology, Shenzhen, China
- Department of Orthopaedics, The Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Baoan District), China, Shenzhen, 518000, China
| | - Defeng Li
- Department of Gastroenterology, Shenzhen People's Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518020, China
| | - Xiaohua Pan
- Department of Orthopaedics, The Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Baoan District), China, Shenzhen, 518000, China.
| | - Yujie Liang
- Department of Orthopaedics, The Second Affiliated Hospital of Shenzhen University (People's Hospital of Shenzhen Baoan District), China, Shenzhen, 518000, China.
- Department of Child and Adolescent Psychiatry, Shenzhen Kangning Hospital, Shenzhen Institute of Mental Health, Shenzhen Mental Health Center, Shenzhen Clinical Research Center for Mental Disorders, Shenzhen, 518020, Guangdong, China.
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Yanatori I, Kishi F, Toyokuni S. New iron export pathways acting via holo-ferritin secretion. Arch Biochem Biophys 2023; 746:109737. [PMID: 37683905 DOI: 10.1016/j.abb.2023.109737] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 08/30/2023] [Accepted: 09/02/2023] [Indexed: 09/10/2023]
Abstract
Ferritin is a spherical nanocage protein for iron storage, composed of 24 light- or heavy-polypeptide chain subunits. A single ferritin molecule can carry up to 4500 iron atoms in its core, which plays an important role in suppressing intracellular iron toxicity. Serum ferritin levels are used as a marker for the total amount of iron stored in the body. Most serum ferritin is iron-free (apo-ferritin) and it is unclear how ferritin is released from cells. Ferritin is secreted into serum via extracellular vesicles (EVs) or the secretory autophagy pathway but not via the classical endoplasmic reticulum (ER)-to-Golgi secretion pathway. We recently discovered that the level of tetraspanin CD63, a common EV marker, is post-transcriptionally regulated by the intracellular iron level and both CD63 and ferritin expression is induced by iron loading. Ferritin is incorporated into CD63(+)-EVs through the ferritin-specific autophagy adapter molecule, NCOA4, and then secreted from cells. EV production differs drastically depending on cell type and physiological conditions. Extracellular matrix detached cells express pentaspanin prominin 2 and prominin 2(+)-EVs secrete ferritin independently of NCOA4 trafficking. Ferritin is tightly bound to iron in EVs and functions as an iron-carrier protein in the extracellular environment. Cells can suppress ferroptosis by secreting holo-ferritin, which reduces intracellular iron concentration. However, this exposes the neighboring cells receiving the secreted holo-ferritin to a large excess of iron. This results in cellular toxicity through increased generation of reactive oxygen species (ROS). Here we review the machinery by which ferritin is incorporated into EVs and its role as an intercellular communication molecule.
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Affiliation(s)
- Izumi Yanatori
- Department of Molecular and Cellular Physiology, Graduate School of Medicine, Kyoto University, Kyoto, 606-8501, Japan.
| | - Fumio Kishi
- Kenjinkai Healthcare Corporation, Yamaguchi, 757-0001, Japan
| | - Shinya Toyokuni
- Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, 65 Tsurumai-Cho, Showa-ku, Nagoya, 466-8550, Japan; Center for Low-temperature Plasma Sciences, Nagoya University, Furo-Cho, Chikusa-ku, Nagoya, 464-8603, Japan
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Stajano D, Lombino FL, Schweizer M, Glatzel M, Saftig P, Gromova KV, Kneussel M. Tetraspanin 15 depletion impairs extracellular vesicle docking at target neurons. JOURNAL OF EXTRACELLULAR BIOLOGY 2023; 2:e113. [PMID: 38938373 PMCID: PMC11080857 DOI: 10.1002/jex2.113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Revised: 08/11/2023] [Accepted: 08/30/2023] [Indexed: 06/29/2024]
Abstract
Neurons in the central nervous system release extracellular vesicles (EVs) and exosomes in response to synaptic activity to regulate physiological processes at target neurons. The intercellular transfer of proteins, mRNAs, lipids or metabolites through EVs potentially modulates the structure and function of neurons and circuits. Whereas the biogenesis of EVs, their release from donor cells, and their molecular composition have been studied extensively, the critical factors and mechanisms regulating EV interactions with target cells are incompletely understood. Here, we identified tetraspanin 15 (Tspan15) as a component of tumor susceptibility gene 101 protein (TSG101)- and CD81-positive EV fractions. Tspan15 fluorescent fusion proteins were released from donor cells and interacted with target cells together with the exosomal marker CD63. EVs collected from wildtype cortical neurons (WT-EVs) underwent similar association with target neurons derived from either wildtype (+/+) or Tspan15 knockout (-/-) mice. In contrast, target cell interactions of EVs collected from Tspan15 (-/-) cortical donor neurons (KO-EVs) were significantly impaired, as compared to WT-EVs. Our data suggest that Tspan15 is dispensable at target neuron plasma membranes, but is required at the EV surface to promote EV docking at target neurons.
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Affiliation(s)
- Daniele Stajano
- Institute of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNHUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Franco L. Lombino
- Institute of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNHUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Michaela Schweizer
- Core Facility Morphology, Center for Molecular Neurobiology, ZMNHUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Markus Glatzel
- Institute of NeuropathologyUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Paul Saftig
- Biochemical InstituteChristian‐Albrechts‐University KielKielGermany
| | - Kira V. Gromova
- Institute of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNHUniversity Medical Center Hamburg‐EppendorfHamburgGermany
| | - Matthias Kneussel
- Institute of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNHUniversity Medical Center Hamburg‐EppendorfHamburgGermany
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van de Wakker SI, Meijers FM, Sluijter JPG, Vader P. Extracellular Vesicle Heterogeneity and Its Impact for Regenerative Medicine Applications. Pharmacol Rev 2023; 75:1043-1061. [PMID: 37280097 DOI: 10.1124/pharmrev.123.000841] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2023] [Revised: 04/20/2023] [Accepted: 05/01/2023] [Indexed: 06/08/2023] Open
Abstract
Extracellular vesicles (EVs) are cell-derived membrane-enclosed particles that are involved in physiologic and pathologic processes. EVs are increasingly being studied for therapeutic applications in the field of regenerative medicine. Therapeutic application of stem cell-derived EVs has shown great potential to stimulate tissue repair. However, the exact mechanisms through which they induce this effect have not been fully clarified. This may to a large extent be attributed to a lack of knowledge on EV heterogeneity. Recent studies suggest that EVs represent a heterogeneous population of vesicles with distinct functions. The heterogeneity of EVs can be attributed to differences in their biogenesis, and as such, they can be classified into distinct populations that can then be further subcategorized into various subpopulations. A better understanding of EV heterogeneity is crucial for elucidating their mechanisms of action in tissue regeneration. This review provides an overview of the latest insights on EV heterogeneity related to tissue repair, including the different characteristics that contribute to such heterogeneity and the functional differences among EV subtypes. It also sheds light on the challenges that hinder clinical translation of EVs. Additionally, innovative EV isolation techniques for studying EV heterogeneity are discussed. Improved knowledge of active EV subtypes would promote the development of tailored EV therapies and aid researchers in the translation of EV-based therapeutics to the clinic. SIGNIFICANCE STATEMENT: Within this review we discuss the differences in regenerative properties of extracellular vesicle (EV) subpopulations and implications of EV heterogeneity for development of EV-based therapeutics. We aim to provide new insights into which aspects are leading to heterogeneity in EV preparations and stress the importance of EV heterogeneity studies for clinical applications.
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Affiliation(s)
- Simonides Immanuel van de Wakker
- Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, The Netherlands (S.I.V.D.W., F.M.M., J.P.G.S., P.V.) and CDL Research, University Medical Center Utrecht, The Netherlands (P.V.)
| | - Fleur Michelle Meijers
- Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, The Netherlands (S.I.V.D.W., F.M.M., J.P.G.S., P.V.) and CDL Research, University Medical Center Utrecht, The Netherlands (P.V.)
| | - Joost Petrus Gerardus Sluijter
- Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, The Netherlands (S.I.V.D.W., F.M.M., J.P.G.S., P.V.) and CDL Research, University Medical Center Utrecht, The Netherlands (P.V.)
| | - Pieter Vader
- Department of Experimental Cardiology, University Medical Center Utrecht, Utrecht University, The Netherlands (S.I.V.D.W., F.M.M., J.P.G.S., P.V.) and CDL Research, University Medical Center Utrecht, The Netherlands (P.V.)
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Lee ES, Ko H, Kim CH, Kim HC, Choi SK, Jeong SW, Lee SG, Lee SJ, Na HK, Park JH, Shin JM. Disease-microenvironment modulation by bare- or engineered-exosome for rheumatoid arthritis treatment. Biomater Res 2023; 27:81. [PMID: 37635253 PMCID: PMC10464174 DOI: 10.1186/s40824-023-00418-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2023] [Accepted: 08/13/2023] [Indexed: 08/29/2023] Open
Abstract
BACKGROUND Exosomes are extracellular vesicles secreted by eukaryotic cells and have been extensively studied for their surface markers and internal cargo with unique functions. A deeper understanding of exosomes has allowed their application in various research areas, particularly in diagnostics and therapy. MAIN BODY Exosomes have great potential as biomarkers and delivery vehicles for encapsulating therapeutic cargo. However, the limitations of bare exosomes, such as rapid phagocytic clearance and non-specific biodistribution after injection, pose significant challenges to their application as drug delivery systems. This review focuses on exosome-based drug delivery for treating rheumatoid arthritis, emphasizing pre/post-engineering approaches to overcome these challenges. CONCLUSION This review will serve as an essential resource for future studies to develop novel exosome-based therapeutic approaches for rheumatoid arthritis. Overall, the review highlights the potential of exosomes as a promising therapeutic approach for rheumatoid arthritis treatment.
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Affiliation(s)
- Eun Sook Lee
- Safety Measurement Institute, Korea Research Institute of Standards and Science (KRISS), 267 Gajeong-Ro, Yuseong-Gu, Daejeon, 34113, Republic of Korea
| | - Hyewon Ko
- Bionanotechnology Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB), Yuseong-Gu, Daejeon, 34141, Republic of Korea
| | - Chan Ho Kim
- School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Hyun-Chul Kim
- Division of Biotechnology, Convergence Research Institute, DGIST, 333 Techno Jungang-Daero, Daegu, 42988, Republic of Korea
| | - Seong-Kyoon Choi
- Division of Biotechnology, Convergence Research Institute, DGIST, 333 Techno Jungang-Daero, Daegu, 42988, Republic of Korea
| | - Sang Won Jeong
- Division of Biotechnology, Convergence Research Institute, DGIST, 333 Techno Jungang-Daero, Daegu, 42988, Republic of Korea
| | - Se-Guen Lee
- Division of Biotechnology, Convergence Research Institute, DGIST, 333 Techno Jungang-Daero, Daegu, 42988, Republic of Korea
| | - Sung-Jun Lee
- Division of Biotechnology, Convergence Research Institute, DGIST, 333 Techno Jungang-Daero, Daegu, 42988, Republic of Korea
| | - Hee-Kyung Na
- Safety Measurement Institute, Korea Research Institute of Standards and Science (KRISS), 267 Gajeong-Ro, Yuseong-Gu, Daejeon, 34113, Republic of Korea
| | - Jae Hyung Park
- School of Chemical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea
| | - Jung Min Shin
- Division of Biotechnology, Convergence Research Institute, DGIST, 333 Techno Jungang-Daero, Daegu, 42988, Republic of Korea.
- Department of Polymer Science and Engineering, Korea National University of Transportation, Chungju, 27469, Republic of Korea.
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Cuadrado-Payán E, Ramírez-Bajo MJ, Bañón-Maneus E, Rovira J, Diekmann F, Revuelta I, Cucchiari D. Physiopathological role of extracellular vesicles in alloimmunity and kidney transplantation and their use as biomarkers. Front Immunol 2023; 14:1154650. [PMID: 37662919 PMCID: PMC10469977 DOI: 10.3389/fimmu.2023.1154650] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 07/21/2023] [Indexed: 09/05/2023] Open
Abstract
Antibody-mediated rejection is the leading cause of kidney graft dysfunction. The process of diagnosing it requires the performance of an invasive biopsy and subsequent histological examination. Early and sensitive biomarkers of graft damage and alloimmunity are needed to identify graft injury and eventually limit the need for a kidney biopsy. Moreover, other scenarios such as delayed graft function or interstitial fibrosis and tubular atrophy face the same problem. In recent years, interest has grown around extracellular vesicles, specifically exosomes actively secreted by immune cells, which are intercellular communicators and have shown biological significance. This review presents their potential as biomarkers in kidney transplantation and alloimmunity.
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Affiliation(s)
- Elena Cuadrado-Payán
- Department of Nephrology and Kidney Transplantation, Hospital Clínic, Barcelona, Spain
- Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi I Sunyer (FRCB-IDIBAPS), Barcelona, Spain
| | - María José Ramírez-Bajo
- Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi I Sunyer (FRCB-IDIBAPS), Barcelona, Spain
- Red de Investigación Renal (REDINREN), Insituto de Salud Carlos III, Madrid, Spain
| | - Elisenda Bañón-Maneus
- Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi I Sunyer (FRCB-IDIBAPS), Barcelona, Spain
- Red de Investigación Renal (REDINREN), Insituto de Salud Carlos III, Madrid, Spain
| | - Jordi Rovira
- Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi I Sunyer (FRCB-IDIBAPS), Barcelona, Spain
- Red de Investigación Renal (REDINREN), Insituto de Salud Carlos III, Madrid, Spain
| | - Fritz Diekmann
- Department of Nephrology and Kidney Transplantation, Hospital Clínic, Barcelona, Spain
- Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi I Sunyer (FRCB-IDIBAPS), Barcelona, Spain
- Red de Investigación Renal (REDINREN), Insituto de Salud Carlos III, Madrid, Spain
| | - Ignacio Revuelta
- Department of Nephrology and Kidney Transplantation, Hospital Clínic, Barcelona, Spain
- Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi I Sunyer (FRCB-IDIBAPS), Barcelona, Spain
- Red de Investigación Renal (REDINREN), Insituto de Salud Carlos III, Madrid, Spain
| | - David Cucchiari
- Department of Nephrology and Kidney Transplantation, Hospital Clínic, Barcelona, Spain
- Laboratori Experimental de Nefrologia I Trasplantament (LENIT), Fundació de Recerca Clínic Barcelona-Institut d’Investigacions Biomèdiques August Pi I Sunyer (FRCB-IDIBAPS), Barcelona, Spain
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Zhou Y, Dong Y, Zhang A, Wu J, Sun Q. The role of mesenchymal stem cells derived exosomes as a novel nanobiotechnology target in the diagnosis and treatment of cancer. Front Bioeng Biotechnol 2023; 11:1214190. [PMID: 37662434 PMCID: PMC10470003 DOI: 10.3389/fbioe.2023.1214190] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2023] [Accepted: 08/03/2023] [Indexed: 09/05/2023] Open
Abstract
Mesenchymal stem cells (MSCs), one of the most common types of stem cells, are involved in the modulation of the tumor microenvironment (TME). With the advancement of nanotechnology, exosomes, especially exosomes secreted by MSCs, have been found to play an important role in the initiation and development of tumors. In recent years, nanobiotechnology and bioengineering technology have been gradually developed to detect and identify exosomes for diagnosis and modify exosomes for tumor treatment. Several novel therapeutic strategies bioengineer exosomes to carry drugs, proteins, and RNAs, and further deliver their encapsulated cargoes to cancer cells through the properties of exosomes. The unique properties of exosomes in cancer treatment include targeting, low immunogenicity, flexibility in modification, and high biological barrier permeability. Nevertheless, the current comprehensive understanding of the roles of MSCs and their secreted exosomes in cancer development remain inadequate. It is necessary to better understand/update the mechanism of action of MSCs-secreted exosomes in cancer development, providing insights for better modification of exosomes through bioengineering technology and nanobiotechnology. Therefore, this review focuses on the role of MSCs-secreted exosomes and bioengineered exosomes in the development, progression, diagnosis, and treatment of cancer.
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Affiliation(s)
- You Zhou
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Yuqing Dong
- China Medical University and Department of Pathology, Shenyang, China
| | - Aixue Zhang
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Jibin Wu
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, China
| | - Qiang Sun
- Department of Plastic Surgery, The First Hospital of China Medical University, Shenyang, China
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