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Sigaroodi F, Jalali Monfared M, Foroutan Koudehi M, Zibaseresht R. Electrospun Decellularized Skeletal Muscle Tissue/Polycaprolactone/Polyaniline as a Potential Scaffold for Muscle Tissue Engineering. J Biomed Mater Res A 2025; 113. [PMID: 40292658 DOI: 10.1002/jbm.a.37920] [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: 12/23/2024] [Revised: 04/10/2025] [Accepted: 04/17/2025] [Indexed: 04/30/2025]
Abstract
Skeletal muscle tissue is capable of self-healing on a small scale. However, during extensive trauma or surgery, regenerative capacities are lost due to the loss of muscle cells and extracellular matrix. Therefore, the development of tissue engineering strategies for the regeneration of muscle tissue should be considered. In this study, we electrospun decellularized skeletal muscle tissue (DSM)/polycaprolactone (PCL)/polyaniline (PANi) as a bioactive polymer composite and investigated the structural characteristics, physicochemical properties, and effect of PANi on these properties. Next, the biological and myogenic effects of scaffolds on human Wharton's jelly mesenchymal stem cells (hWJ-MSCs) were investigated. The results showed that DSM/PCL/PANi is a conductive fibrous scaffold with favorable physical and chemical properties for muscle tissue engineering; it is biocompatible with hWJ-MSCs and stimulates their morphology. Additionally, hWJ-MSCs cultured on DSM/PCL/PANi showed a significant increase in the expression of MyoD, Myogenin, and MHC. Laboratory experiments showed that the electrospun scaffold of DSM/PCL/PANi is biocompatible with favorable physical properties for the growth of stem cells and the expression of myogenic markers, which can be useful in the development of biological scaffold approaches for muscle tissue engineering.
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Affiliation(s)
- Faraz Sigaroodi
- Biomaterials and Medicinal Chemistry Research Center, Aja University of Medical Sciences, Tehran, Iran
| | - Marziyeh Jalali Monfared
- Biomaterials and Medicinal Chemistry Research Center, Aja University of Medical Sciences, Tehran, Iran
| | - Masoumeh Foroutan Koudehi
- Biomaterials and Medicinal Chemistry Research Center, Aja University of Medical Sciences, Tehran, Iran
| | - Ramin Zibaseresht
- Biomaterials and Medicinal Chemistry Research Center, Aja University of Medical Sciences, Tehran, Iran
- Department of Chemistry and Physics, Faculty of Sciences, Maritime University of Imam Khomeini, Nowshahr, Iran
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2
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Tobo C, Jain A, Gamage ME, Jelliss P, Garg K. Electrostatic Gelatin Nanoparticles for Biotherapeutic Delivery. Gels 2024; 10:757. [PMID: 39727515 DOI: 10.3390/gels10120757] [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: 11/04/2024] [Revised: 11/19/2024] [Accepted: 11/20/2024] [Indexed: 12/28/2024] Open
Abstract
Biological agents such as extracellular vesicles (EVs) and growth factors, when administered in vivo, often face rapid clearance, limiting their therapeutic potential. To address this challenge and enhance their efficacy, we propose the electrostatic conjugation and sequestration of these agents into gelatin-based biomaterials. In this study, gelatin nanoparticles (GNPs) were synthesized via the nanoprecipitation method, with adjustments to the pH of the gelatin solution (4.0 or 10.0) to introduce either a positive or negative charge to the nanoparticles. The GNPs were characterized using dynamic light scattering (DLS), X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and Transmission electron microscopy (TEM) imaging. Both positively and negatively charged GNPs were confirmed to be endotoxin-free and non-cytotoxic. Mesenchymal stem cell (MSC)-derived EVs exhibited characteristic surface markers and a notable negative charge. Zeta potential measurements validated the electrostatic conjugation of MSC-EVs with positively charged GNPs. Utilizing a transwell culture system, we evaluated the impact of EV-GNP conjugates encapsulated within a gelatin hydrogel on macrophage secretory activity. The results demonstrated the bioactivity of EV-GNP conjugates and their synergistic effect on macrophage secretome over five days of culture. In summary, these findings demonstrate the efficacy of electrostatically coupled biotherapeutics with biomaterials for tissue regeneration applications.
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Affiliation(s)
- Connor Tobo
- Biomedical Engineering Department, Saint Louis University, Saint Louis, MO 63103, USA
| | - Avantika Jain
- Pharmacology and Physiology Department, Saint Louis University, Saint Louis, MO 63104, USA
| | | | - Paul Jelliss
- Chemistry Department, Saint Louis University, Saint Louis, MO 63103, USA
| | - Koyal Garg
- Biomedical Engineering Department, Saint Louis University, Saint Louis, MO 63103, USA
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Gyllenhammer LE, Zaegel V, Duensing AM, Lixandrao ME, Dabelea D, Bergman BC, Boyle KE. Lipidomics of infant mesenchymal stem cells associate with the maternal milieu and child adiposity. JCI Insight 2024; 9:e180016. [PMID: 39226911 PMCID: PMC11466181 DOI: 10.1172/jci.insight.180016] [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: 02/05/2024] [Accepted: 08/21/2024] [Indexed: 09/05/2024] Open
Abstract
Our objective was to interrogate mesenchymal stem cell (MSC) lipid metabolism and gestational exposures beyond maternal body mass that may contribute to child obesity risk. MSCs were cultured from term infants of mothers with obesity (n = 16) or normal weight (n = 15). In MSCs undergoing myogenesis in vitro, we used lipidomics to distinguish phenotypes by unbiased cluster analysis and lipid challenge (24-hour excess fatty acid [24hFA]). We measured MSC AMP-activated protein kinase (AMPK) activity and fatty acid oxidation (FAO), and a composite index of maternal glucose, insulin, triglycerides, free fatty acids, TNF-α, and high-density lipoprotein and total cholesterol in fasting blood from mid and late gestation (~17 and ~27 weeks, respectively). We measured child adiposity at birth (n = 29), 4-6 months (n = 29), and 4-6 years (n = 13). Three MSC clusters were distinguished by triacylglycerol (TAG) stores, with greatest TAGs in Cluster 2. All clusters increased acylcarnitines and TAGs with 24hFA, although Cluster 2 was more pronounced and corresponded to AMPK activation and FAO. Maternal metabolic markers predicted MSC clusters and child adiposity at 4-6 years (both highest in Cluster 3). Our data support the notion that MSC phenotypes are predicted by comprehensive maternal metabolic milieu exposures, independent of maternal BMI, and suggest utility as an at-birth predictor for child adiposity, although validation with larger longitudinal samples is warranted.
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Affiliation(s)
- Lauren E. Gyllenhammer
- Department of Pediatrics, University of California, Irvine, School of Medicine, Irvine, California, USA
| | - Vincent Zaegel
- Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Allison M. Duensing
- Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Manoel E. Lixandrao
- Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Dana Dabelea
- The Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Aurora, Colorado, USA
- Department of Epidemiology, Colorado School of Public Health
- Department of Pediatrics, and
| | - Bryan C. Bergman
- Department of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
| | - Kristen E. Boyle
- Department of Pediatrics, Section of Nutrition, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
- The Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Aurora, Colorado, USA
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Younesi FS, Hinz B. The Myofibroblast Fate of Therapeutic Mesenchymal Stromal Cells: Regeneration, Repair, or Despair? Int J Mol Sci 2024; 25:8712. [PMID: 39201399 PMCID: PMC11354465 DOI: 10.3390/ijms25168712] [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: 06/21/2024] [Revised: 07/31/2024] [Accepted: 08/06/2024] [Indexed: 09/02/2024] Open
Abstract
Mesenchymal stromal cells (MSCs) can be isolated from various tissues of healthy or patient donors to be retransplanted in cell therapies. Because the number of MSCs obtained from biopsies is typically too low for direct clinical application, MSC expansion in cell culture is required. However, ex vivo amplification often reduces the desired MSC regenerative potential and enhances undesired traits, such as activation into fibrogenic myofibroblasts. Transiently activated myofibroblasts restore tissue integrity after organ injury by producing and contracting extracellular matrix into scar tissue. In contrast, persistent myofibroblasts cause excessive scarring-called fibrosis-that destroys organ function. In this review, we focus on the relevance and molecular mechanisms of myofibroblast activation upon contact with stiff cell culture plastic or recipient scar tissue, such as hypertrophic scars of large skin burns. We discuss cell mechanoperception mechanisms such as integrins and stretch-activated channels, mechanotransduction through the contractile actin cytoskeleton, and conversion of mechanical signals into transcriptional programs via mechanosensitive co-transcription factors, such as YAP, TAZ, and MRTF. We further elaborate how prolonged mechanical stress can create persistent myofibroblast memory by direct mechanotransduction to the nucleus that can evoke lasting epigenetic modifications at the DNA level, such as histone methylation and acetylation. We conclude by projecting how cell culture mechanics can be modulated to generate MSCs, which epigenetically protected against myofibroblast activation and transport desired regeneration potential to the recipient tissue environment in clinical therapies.
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Affiliation(s)
- Fereshteh Sadat Younesi
- Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada;
- Keenan Research Institute for Biomedical Science, St. Michael’s Hospital, Toronto, ON M5B 1T8, Canada
| | - Boris Hinz
- Faculty of Dentistry, University of Toronto, Toronto, ON M5G 1G6, Canada;
- Keenan Research Institute for Biomedical Science, St. Michael’s Hospital, Toronto, ON M5B 1T8, Canada
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Koung Ngeun S, Shimizu M, Kaneda M. Injection of Adipose-Derived Mesenchymal Stem/Stromal Cells Suppresses Muscle Atrophy Markers and Adipogenic Markers in a Rat Fatty Muscle Degeneration Model. Curr Issues Mol Biol 2024; 46:7877-7894. [PMID: 39194684 DOI: 10.3390/cimb46080467] [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: 06/28/2024] [Revised: 07/17/2024] [Accepted: 07/22/2024] [Indexed: 08/29/2024] Open
Abstract
Fatty muscle degeneration and muscle atrophy have not been successfully treated due to their irreversible pathology. This study evaluated the efficacy of rat adipose-derived mesenchymal stem/stromal cells (ADP MSCs) in treating fatty muscle degeneration (FD). A total of 36 rats were divided into three groups: the control (C) group (n = 12); FD model group, generated by sciatic nerve crushing (n = 12); and the group receiving ADP MSC treatment for FD (FD+MSCs) (n = 12). In Group FD+MSCs, ADP MSCs were injected locally into the gastrocnemius muscle one week after the FD model was created (Day 8). On Day 22 (n = 18) and Day 43 (n = 18), muscle morphology, histopathology, and molecular analyses (inflammation, muscle atrophy, adipocytes, and muscle differentiation markers) were performed. In Group FD+MSCs, the formation of immature myofibers was observed on Day 22, and mitigation of fatty degeneration and muscle atrophy progression was evident on Day 43. Gene expression of muscle atrophy markers (FBXO32, TRIM63, and FOXO1) and adipogenic markers (ADIPOQ, PPARG, FABP4, and PDGFRA) was lower in Group FD+MSCs than Group FD on Day 43. ADP MSCs induce anti-inflammatory effects, inhibit fat accumulation, and promote muscle regeneration, highlighting their potential as promising therapy for FD and atrophy.
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Affiliation(s)
- Sai Koung Ngeun
- Department of Veterinary Diagnostic Imaging, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu 183-8509, Tokyo, Japan
| | - Miki Shimizu
- Department of Veterinary Diagnostic Imaging, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu 183-8509, Tokyo, Japan
| | - Masahiro Kaneda
- Department of Veterinary Anatomy, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu 183-8509, Tokyo, Japan
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Koung Ngeun S, Shimizu M, Kaneda M. Myogenic Differentiation and Immunomodulatory Properties of Rat Adipose-Derived Mesenchymal Stem/Stromal Cells. BIOLOGY 2024; 13:72. [PMID: 38392291 PMCID: PMC10886144 DOI: 10.3390/biology13020072] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Revised: 01/19/2024] [Accepted: 01/24/2024] [Indexed: 02/24/2024]
Abstract
The myogenic differentiation potential of MSCs is a key factor in their potential use as a cell source for muscle tissue repair and regeneration. Additionally, evaluating the immunomodulatory properties of MSCs is important to highlight their potential for regulating inflammation and supporting tissue regeneration. Given the limited literature on muscle differentiation potential and immunomodulatory properties, this study aims to characterize rat ADP MSCs for treating muscle disease. We isolated MSCs from adipose tissues around the periscapular region of the rats. We used a monoculture method for the myogenic differentiation and modified the myogenic induction medium by supplementing it with the growth factors FGF, HGF, and IGF. In rat ADP MSCs, expression of the MSC-specific marker, CD90, was 87.7%, while CD44 was 42.8%. For genes involved in immunomodulation, IGF1 and TGFB1 were highly expressed, while IL6 was poorly expressed. In addition to their trilineage differentiation potential, ADP MSCs exhibited the capacity to differentiate into myogenic cell lines, as evidenced by changes in cell morphology, leading to elongated and aligned structures and the expression of the MyoD and MYOG antibodies. The study found that ADP MSCs show great clinical promise for muscle regeneration.
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Affiliation(s)
- Sai Koung Ngeun
- Laboratory of Veterinary Diagnostic Imaging, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan
| | - Miki Shimizu
- Laboratory of Veterinary Diagnostic Imaging, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan
| | - Masahiro Kaneda
- Laboratory of Veterinary Anatomy, Faculty of Agriculture, Tokyo University of Agriculture and Technology, 3-5-8 Saiwai-cho, Fuchu, Tokyo 183-8509, Japan
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Zhang H, Gu Y, Zhang K, Tu Y, Ouyang C. Roles and mechanisms of umbilical cord mesenchymal stem cells in the treatment of diabetic foot: A review of preclinical and clinical studies. J Diabetes Complications 2024; 38:108671. [PMID: 38154217 DOI: 10.1016/j.jdiacomp.2023.108671] [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: 09/05/2023] [Revised: 11/29/2023] [Accepted: 12/17/2023] [Indexed: 12/30/2023]
Abstract
AIMS Growing preclinical and clinical evidence has suggested the potential method of umbilical cord mesenchymal stem cell (UCMSC) therapy for diabetic foot. Thus, the authors provided an outline of the application of UCMSCs in the treatment of diabetic foot and further summarized the roles and mechanisms of this therapy. DATA SYNTHESIS With no time limitations, the authors searched the Web of Science, Cochrane Central Register of Controlled Trials, and PubMed (MEDLINE) databases. 14 studies were included, including 9 preclinical experiments and 5 clinical trials (3 RCTs and 2 single-arm trials). CONCLUSIONS The UCMSCs are of great efficacy and safety, and function mainly by reducing inflammation, regulating immunity, promoting growth factors, and enhancing the functions of vascular endothelial cells, fibroblasts, and keratinocytes. As a result, ulcer healing-related biological processes ensue, which finally lead to diabetic foot ulcer healing and clinical symptom improvement. UCMSC treatment enhances diabetic foot ulcer healing and has a safety profile. They function mainly by modulating immunity, promoting growth factor secretion, and enhancing cellular functions. More well-designed preclinical and clinical studies are needed to provide the most optimal protocol, the comprehensive molecular mechanisms, as well as to further evaluate the efficiency and safety profile of UCMSC treatment in diabetic foot patients.
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Affiliation(s)
- Haorui Zhang
- Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xi Cheng District, Beijing 100037, China
| | - Yuanrui Gu
- Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xi Cheng District, Beijing 100037, China
| | - Ke Zhang
- Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xi Cheng District, Beijing 100037, China
| | - Yanxia Tu
- Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xi Cheng District, Beijing 100037, China
| | - Chenxi Ouyang
- Department of Vascular Surgery, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167 Beilishi Road, Xi Cheng District, Beijing 100037, China.
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Seyyedin S, Ezzatabadipour M, Nematollahi-Mahani SN. The Role of Various Factors in Neural Differentiation of Human Umbilical Cord Mesenchymal Stem Cells with a Special Focus on the Physical Stimulants. Curr Stem Cell Res Ther 2024; 19:166-177. [PMID: 36734908 DOI: 10.2174/1574888x18666230124151311] [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: 07/03/2022] [Revised: 10/05/2022] [Accepted: 11/25/2022] [Indexed: 02/04/2023]
Abstract
Human umbilical cord matrix-derived mesenchymal stem cells (hUCMs) are considered as ideal tools for cell therapy procedures and regenerative medicine. The capacity of these cells to differentiate into neural lineage cells make them potentially important in the treatment of various neurodegenerative diseases. An electronic search was performed in Web of Science, PubMed/MEDLINE, Scopus and Google Scholar databases for articles published from January 1990 to March 2022. This review discusses the current knowledge on the effect of various factors, including physical, chemical and biological stimuli which play a key role in the differentiation of hUCMs into neural and glial cells. Moreover, the currently understood molecular mechanisms involved in the neural differentiation of hUCMs under various environmental stimuli are reviewed. Various stimuli, especially physical stimuli and specifically different light sources, have revealed effects on neural differentiation of mesenchymal stem cells, including hUCMs; however, due to the lack of information about the exact mechanisms, there is still a need to find optimal conditions to promote the differentiation capacity of these cells which in turn can lead to significant progress in the clinical application of hUCMs for the treatment of neurological disorders.
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Affiliation(s)
- Sajad Seyyedin
- Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
| | - Massood Ezzatabadipour
- Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
- Physiology Research Center, Kerman University of Medical Sciences, Kerman, Iran
| | - Seyed Noureddin Nematollahi-Mahani
- Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
- Neuroscience Research Center, Kerman University of Medical Sciences, Kerman, Iran
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Haleem A, Pan JM, Shah A, Hussain H, He WD. A systematic review on new advancement and assessment of emerging polymeric cryogels for environmental sustainability and energy production. Sep Purif Technol 2023. [DOI: 10.1016/j.seppur.2023.123678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
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Stage HJ, Trappe S, Söllig K, Trachsel DS, Kirsch K, Zieger C, Merle R, Aschenbach JR, Gehlen H. Multilineage Differentiation Potential of Equine Adipose-Derived Stromal/Stem Cells from Different Sources. Animals (Basel) 2023; 13:ani13081352. [PMID: 37106915 PMCID: PMC10135324 DOI: 10.3390/ani13081352] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 04/06/2023] [Accepted: 04/13/2023] [Indexed: 04/29/2023] Open
Abstract
The investigation of multipotent stem/stromal cells (MSCs) in vitro represents an important basis for translational studies in large animal models. The study's aim was to examine and compare clinically relevant in vitro properties of equine MSCs, which were isolated from abdominal (abd), retrobulbar (rb) and subcutaneous (sc) adipose tissue by collagenase digestion (ASCs-SVF) and an explant technique (ASCs-EXP). Firstly, we examined proliferation and trilineage differentiation and, secondly, the cardiomyogenic differentiation potential using activin A, bone morphogenetic protein-4 and Dickkopf-1. Fibroblast-like, plastic-adherent ASCs-SVF and ASCs-EXP were obtained from all sources. The proliferation and chondrogenic differentiation potential did not differ significantly between the isolation methods and localizations. However, abd-ASCs-EXP showed the highest adipogenic differentiation potential compared to rb- and sc-ASCs-EXP on day 7 and abd-ASCs-SVF a higher adipogenic potential compared to abd-ASCs-EXP on day 14. Osteogenic differentiation potential was comparable at day 14, but by day 21, abd-ASCs-EXP demonstrated a higher osteogenic potential compared to abd-ASCs-SVF and rb-ASCs-EXP. Cardiomyogenic differentiation could not be achieved. This study provides insight into the proliferation and multilineage differentiation potential of equine ASCs and is expected to provide a basis for future preclinical and clinical studies in horses.
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Affiliation(s)
- Hannah J Stage
- Equine Clinic, Surgery and Radiology, Department of Veterinary Medicine, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Susanne Trappe
- Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Katharina Söllig
- Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Dagmar S Trachsel
- Clinical Unit of Equine Internal Medicine, Department for Companion Animals and Horses, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria
| | - Katharina Kirsch
- Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Cornelia Zieger
- Institute of Veterinary Pathology Department of Veterinary Medicine, Freie Universität Berlin, Robert-von-Ostertag-Straße 15, 14163 Berlin, Germany
| | - Roswitha Merle
- Institute for Veterinary Epidemiology and Biostatistics, Department of Veterinary Medicine, Freie Universität Berlin, Königsweg 67, 14163 Berlin, Germany
| | - Jörg R Aschenbach
- Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
| | - Heidrun Gehlen
- Equine Clinic, Surgery and Radiology, Department of Veterinary Medicine, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, Germany
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Koken GY, Abamor ES, Allahverdiyev A, Karaoz E. Wharton Jelly Derived Mesenchymal Stem Cell's Exosomes Demonstrate Significant Antileishmanial and Wound Healing Effects in Combination with Aloe-Emodin: An in Vitro Study. J Pharm Sci 2022; 111:3232-3242. [PMID: 35995206 DOI: 10.1016/j.xphs.2022.08.016] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 08/12/2022] [Accepted: 08/12/2022] [Indexed: 01/05/2023]
Abstract
The aim of the present study was to explore the antileishmanial performance and wound healing effect of exosomes isolated from Wharton Jelly derived mesenchymal stem cells (WJ-MSCs) in combination with aloe-emodin. MSCs obtained from Wharton Jelly were characterized by flow cytometry. Exosomes were isolated from cultivated stem cells by ultacentrifugation method. Scanning Electron Microscopy (SEM), Dynamic Light Scattering (DLS), Nanoparticle Tracking Analysis (NTA) and flow cytometry were used for characterization of obtained exosomes. The cytotoxicities of characterized exosomes and aloe-emodin at different concentrations were investigated on L929 and J774 cell lines. Non-toxic concentrations of each agent were combined and their inhibitory efficacies on L.major promastigotes and amastigotes were investigated by different techniques such as MTT, parasite count and measurements of infection index. Finally, wound healing activities of combinations were examined on in vitro artifical wound model and compared with the use of exosomes alone. According to outcome of flow cytometic analysis, vesicles isolated from WJ-MSCs highly expressed the markers such as CD63 special for exosome profile. SEM and NTA results demonstrated that derived exosomes possessed dimensions between 150 to 200 nanometers and elicited the cup-shape specific to exosomes. Combinations including non-toxic dosages of exosomes and aloe-emodin demonstrated superior antileishmanial effectivenesses both on promastigotes and amastigotes in contrast to use of exosome alone since they lead to inhibition of promastigotes and amastigotes for 4 and 10-folds in comparison to control, respectively. Additionally, combinations elicited more rapidly and effective in vitro wound-healing performance in contrast to use of exosome alone. At the end of 24 h incubation application of combinations gave rise to wound closure at a rate of 72 %, while in the control group 52 % of wound area has not been healed, yet. These results reflect that mentioned combination has great potential to be used in treatment of cutaneus leishmaniasis (CL) since they have magnificient capacity to inhibit Leishmania parasites while enhancing wound healing.
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Affiliation(s)
- Gulnaz Yildirim Koken
- Yildiz Technical University, Department of Bioengineering, Istanbul, Turkey; Center for Regenerative Medicine and Stem Cell Research & Manufacturing (LivMedCell), Istanbul, Turkey
| | - Emrah Sefik Abamor
- Yildiz Technical University, Department of Bioengineering, Istanbul, Turkey
| | - Adil Allahverdiyev
- V. Akhundov National Scientific Research Medical Prophylactic Institute, Baku, Azarrbaijan Republic.
| | - Erdal Karaoz
- Center for Regenerative Medicine and Stem Cell Research & Manufacturing (LivMedCell), Istanbul, Turkey
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12
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Chaves AB, Zheng D, Johnson JA, Bergman BC, Patinkin ZW, Zaegel V, Biagioni EM, Krassovskaia P, Broskey NT, May LE, Dabelea D, Houmard JA, Boyle KE. Infant Mesenchymal Stem Cell Insulin Action Is Associated With Maternal Plasma Free Fatty Acids, Independent of Obesity Status: The Healthy Start Study. Diabetes 2022; 71:1649-1659. [PMID: 35621990 PMCID: PMC9490356 DOI: 10.2337/db21-0812] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 05/16/2022] [Indexed: 11/13/2022]
Abstract
Preclinical rodent and nonhuman primate models investigating maternal obesity have highlighted the importance of the intrauterine environment in the development of insulin resistance in offspring; however, it remains unclear if these findings can be translated to humans. To investigate possible intrauterine effects in humans, we isolated mesenchymal stem cells (MSCs) from the umbilical cord tissue of infants born to mothers of normal weight or mothers with obesity. Insulin-stimulated glycogen storage was determined in MSCs undergoing myogenesis in vitro. There was no difference in insulin action based on maternal obesity. However, maternal free fatty acid (FFA) concentration, cord leptin, and intracellular triglyceride content were positively correlated with insulin action. Furthermore, MSCs from offspring born to mothers with elevated FFAs displayed elevated activation of the mTOR signaling pathway. Taken together, these data suggest that infants born to mothers with elevated lipid availability have greater insulin action in MSCs, which may indicate upregulation of growth and lipid storage pathways during periods of maternal overnutrition.
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Affiliation(s)
- Alec B. Chaves
- Human Performance Laboratory, Department of Kinesiology, East Carolina University, Greenville, NC
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC
| | - Donghai Zheng
- Human Performance Laboratory, Department of Kinesiology, East Carolina University, Greenville, NC
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC
| | - Jonathan A. Johnson
- Human Performance Laboratory, Department of Kinesiology, East Carolina University, Greenville, NC
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC
| | - Bryan C. Bergman
- Division of Endocrinology, Metabolism, and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO
| | - Zachary W. Patinkin
- Department of Obstetrics and Gynecology, University of Rochester Medical Center, Rochester, NY
| | - Vincent Zaegel
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
| | - Ericka M. Biagioni
- Human Performance Laboratory, Department of Kinesiology, East Carolina University, Greenville, NC
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC
| | - Polina Krassovskaia
- Human Performance Laboratory, Department of Kinesiology, East Carolina University, Greenville, NC
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC
| | - Nicholas T. Broskey
- Human Performance Laboratory, Department of Kinesiology, East Carolina University, Greenville, NC
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC
| | - Linda E. May
- Human Performance Laboratory, Department of Kinesiology, East Carolina University, Greenville, NC
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC
| | - Dana Dabelea
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO
- The Lifecourse Epidemiology of Adiposity and Diabetes Center, Aurora, CO
| | - Joseph A. Houmard
- Human Performance Laboratory, Department of Kinesiology, East Carolina University, Greenville, NC
- East Carolina Diabetes and Obesity Institute, East Carolina University, Greenville, NC
| | - Kristen E. Boyle
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO
- The Lifecourse Epidemiology of Adiposity and Diabetes Center, Aurora, CO
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13
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Tan MI, Alfarafisa NM, Septiani P, Barlian A, Firmansyah M, Faizal A, Melani L, Nugrahapraja H. Potential Cell-Based and Cell-Free Therapy for Patients with COVID-19. Cells 2022; 11:2319. [PMID: 35954162 PMCID: PMC9367488 DOI: 10.3390/cells11152319] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 07/20/2022] [Accepted: 07/26/2022] [Indexed: 02/01/2023] Open
Abstract
Since it was first reported, the novel coronavirus disease 2019 (COVID-19) remains an unresolved puzzle for biomedical researchers in different fields. Various treatments, drugs, and interventions were explored as treatments for COVID. Nevertheless, there are no standard and effective therapeutic measures. Meanwhile, mesenchymal stem cell (MSC) therapy offers a new approach with minimal side effects. MSCs and MSC-based products possess several biological properties that potentially alleviate COVID-19 symptoms. Generally, there are three classifications of stem cell therapy: cell-based therapy, tissue engineering, and cell-free therapy. This review discusses the MSC-based and cell-free therapies for patients with COVID-19, their potential mechanisms of action, and clinical trials related to these therapies. Cell-based therapies involve the direct use and injection of MSCs into the target tissue or organ. On the other hand, cell-free therapy uses secreted products from cells as the primary material. Cell-free therapy materials can comprise cell secretomes and extracellular vesicles. Each therapeutic approach possesses different benefits and various risks. A better understanding of MSC-based and cell-free therapies is essential for supporting the development of safe and effective COVID-19 therapy.
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Affiliation(s)
- Marselina Irasonia Tan
- School of Life Sciences and Technology, Institut Teknologi Bandung, Bandung 40132, Indonesia; (P.S.); (A.B.); (M.F.); (A.F.); (L.M.); (H.N.)
| | - Nayla Majeda Alfarafisa
- Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Sumedang 45363, Indonesia;
| | - Popi Septiani
- School of Life Sciences and Technology, Institut Teknologi Bandung, Bandung 40132, Indonesia; (P.S.); (A.B.); (M.F.); (A.F.); (L.M.); (H.N.)
| | - Anggraini Barlian
- School of Life Sciences and Technology, Institut Teknologi Bandung, Bandung 40132, Indonesia; (P.S.); (A.B.); (M.F.); (A.F.); (L.M.); (H.N.)
| | - Mochamad Firmansyah
- School of Life Sciences and Technology, Institut Teknologi Bandung, Bandung 40132, Indonesia; (P.S.); (A.B.); (M.F.); (A.F.); (L.M.); (H.N.)
| | - Ahmad Faizal
- School of Life Sciences and Technology, Institut Teknologi Bandung, Bandung 40132, Indonesia; (P.S.); (A.B.); (M.F.); (A.F.); (L.M.); (H.N.)
| | - Lili Melani
- School of Life Sciences and Technology, Institut Teknologi Bandung, Bandung 40132, Indonesia; (P.S.); (A.B.); (M.F.); (A.F.); (L.M.); (H.N.)
| | - Husna Nugrahapraja
- School of Life Sciences and Technology, Institut Teknologi Bandung, Bandung 40132, Indonesia; (P.S.); (A.B.); (M.F.); (A.F.); (L.M.); (H.N.)
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14
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Biophysical Characterization and Cytocompatibility of Cellulose Cryogels Reinforced with Chitin Nanowhiskers. Polymers (Basel) 2022; 14:polym14132694. [PMID: 35808742 PMCID: PMC9268798 DOI: 10.3390/polym14132694] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 06/28/2022] [Accepted: 06/29/2022] [Indexed: 01/23/2023] Open
Abstract
Polysaccharide-based cryogels are promising materials for producing scaffolds in tissue engineering. In this work, we obtained ultralight (0.046–0.162 g/cm3) and highly porous (88.2–96.7%) cryogels with a complex hierarchical morphology by dissolving cellulose in phosphoric acid, with subsequent regeneration and freeze-drying. The effect of the cellulose dissolution temperature on phosphoric acid and the effect of the freezing time of cellulose hydrogels on the structure and properties of the obtained cryogels were studied. It has been shown that prolonged freezing leads to the formation of denser and stronger cryogels with a network structure. The incorporation of chitin nanowhiskers led to a threefold increase in the strength of the cellulose cryogels. The X-ray diffraction method showed that the regenerated cellulose was mostly amorphous, with a crystallinity of 26.8–28.4% in the structure of cellulose II. Cellulose cryogels with chitin nanowhiskers demonstrated better biocompatibility with mesenchymal stem cells compared to the normal cellulose cryogels.
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15
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Khodayari S, Khodayari H, Ebrahimi-Barough S, Khanmohammadi M, Islam MS, Vesovic M, Goodarzi A, Mahmoodzadeh H, Nayernia K, Aghdami N, Ai J. Stem Cell Therapy in Limb Ischemia: State-of-Art, Perspective, and Possible Impacts of Endometrial-Derived Stem Cells. Front Cell Dev Biol 2022; 10:834754. [PMID: 35676930 PMCID: PMC9168222 DOI: 10.3389/fcell.2022.834754] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 04/11/2022] [Indexed: 11/13/2022] Open
Abstract
As an evidence-based performance, the rising incidence of various ischemic disorders has been observed across many nations. As a result, there is a growing need for the development of more effective regenerative approaches that could serve as main therapeutic strategies for the treatment of these diseases. From a cellular perspective, promoted complex inflammatory mechanisms, after inhibition of organ blood flow, can lead to cell death in all tissue types. In this case, using the stem cell technology provides a safe and regenerative approach for ischemic tissue revascularization and functional cell formation. Limb ischemia (LI) is one of the most frequent ischemic disease types and has been shown to have a promising regenerative response through stem cell therapy based on several clinical trials. Bone marrow-derived mononuclear cells (BM-MNCs), peripheral blood CD34-positive mononuclear cells (CD34+ PB-MNCs), mesenchymal stem cells (MSCs), and endothelial stem/progenitor cells (ESPCs) are the main, well-examined stem cell types in these studies. Additionally, our investigations reveal that endometrial tissue can be considered a suitable candidate for isolating new safe, effective, and feasible multipotent stem cells for limb regeneration. In addition to other teams’ results, our in-depth studies on endometrial-derived stem cells (EnSCs) have shown that these cells have translational potential for limb ischemia treatment. The EnSCs are able to generate diverse types of cells which are essential for limb reconstruction, including endothelial cells, smooth muscle cells, muscle cells, and even peripheral nervous system populations. Hence, the main object of this review is to present stem cell technology and evaluate its method of regeneration in ischemic limb tissue.
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Affiliation(s)
- Saeed Khodayari
- Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran
- Breast Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
- International Center for Personalized Medicine (P7MEDICINE), Düsseldorf, Germany
| | - Hamid Khodayari
- Breast Disease Research Center, Tehran University of Medical Sciences, Tehran, Iran
- International Center for Personalized Medicine (P7MEDICINE), Düsseldorf, Germany
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
| | - Somayeh Ebrahimi-Barough
- Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran
| | - Mehdi Khanmohammadi
- Skull Base Research Center, The Five Senses Institute, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Md Shahidul Islam
- Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran
| | - Miko Vesovic
- Department of Mathematics, Statistics, and Computer Science, University of Illinois at Chicago, Chicago, IL, United States
| | - Arash Goodarzi
- Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran
| | | | - Karim Nayernia
- International Center for Personalized Medicine (P7MEDICINE), Düsseldorf, Germany
| | - Nasser Aghdami
- Department of Regenerative Medicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
- Department of Infectious Diseases and Tropical Medicines, Tehran University of Medical Sciences, Tehran, Iran
- *Correspondence: Jafar Ai, ; Nasser Aghdami,
| | - Jafar Ai
- Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Science, Tehran, Iran
- *Correspondence: Jafar Ai, ; Nasser Aghdami,
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16
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Uyar R. Glioblastoma microenvironment: The stromal interactions. Pathol Res Pract 2022; 232:153813. [PMID: 35228161 DOI: 10.1016/j.prp.2022.153813] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Accepted: 02/22/2022] [Indexed: 12/13/2022]
Abstract
Glioblastomas (GBMs) are the most common primary brain tumors with poor prognosis due to their aggressive growth accompanied by invasive behavior and therapy-resistance. These features promote a high rate of recurrence; therefore, they are largely incurable. One major cause of the incurability is brought about by the intimate relationship of GBM cells with the microenvironment, which supports the tumor growth in various ways by providing a permissive neighborhood. In the tumor microenvironment are glioma stem cells (GSC); endothelial cells (EC) and hypoxic regions; immune cells and immune modulatory cues; astrocytes; neural stem/precursor cells (NPC) and mesenchymal stem cells (MSC). Each cell type contributes to GBM pathology in unique ways; therefore, it is necessary to understand such interactions between GBM cells and the stromal cells in order to establish a through understanding of the GBM pathology. By explaining the contribution of each stromal entity to GBM pathology we aim to draw an interaction map for GBMs and promote awareness of the complexity of the GBM microenvironment.
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Affiliation(s)
- Ramazan Uyar
- Walter Brendel Center of Experimental Medicine, Faculty of Medicine, LMU Munich, Munich, Germany.
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17
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Cellulose Cryogels as Promising Materials for Biomedical Applications. Int J Mol Sci 2022; 23:ijms23042037. [PMID: 35216150 PMCID: PMC8880007 DOI: 10.3390/ijms23042037] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 02/04/2022] [Accepted: 02/11/2022] [Indexed: 02/01/2023] Open
Abstract
The availability, biocompatibility, non-toxicity, and ease of chemical modification make cellulose a promising natural polymer for the production of biomedical materials. Cryogelation is a relatively new and straightforward technique for producing porous light and super-macroporous cellulose materials. The production stages include dissolution of cellulose in an appropriate solvent, regeneration (coagulation) from the solution, removal of the excessive solvent, and then freezing. Subsequent freeze-drying preserves the micro- and nanostructures of the material formed during the regeneration and freezing steps. Various factors can affect the structure and properties of cellulose cryogels, including the cellulose origin, the dissolution parameters, the solvent type, and the temperature and rate of freezing, as well as the inclusion of different fillers. Adjustment of these parameters can change the morphology and properties of cellulose cryogels to impart the desired characteristics. This review discusses the structure of cellulose and its properties as a biomaterial, the strategies for cellulose dissolution, and the factors affecting the structure and properties of the formed cryogels. We focus on the advantages of the freeze-drying process, highlighting recent studies on the production and application of cellulose cryogels in biomedicine and the main cryogel quality characteristics. Finally, conclusions and prospects are presented regarding the application of cellulose cryogels in wound healing, in the regeneration of various tissues (e.g., damaged cartilage, bone tissue, and nerves), and in controlled-release drug delivery.
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18
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Floriano JF, Emanueli C, Vega S, Barbosa AMP, Oliveira RGD, Floriano EAF, Graeff CFDO, Abbade JF, Herculano RD, Sobrevia L, Rudge MVC. Pro-angiogenic approach for skeletal muscle regeneration. Biochim Biophys Acta Gen Subj 2022; 1866:130059. [PMID: 34793875 DOI: 10.1016/j.bbagen.2021.130059] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 11/01/2021] [Indexed: 12/19/2022]
Abstract
The angiogenesis process is a phenomenon in which numerous molecules participate in the stimulation of the new vessels' formation from pre-existing vessels. Angiogenesis is a crucial step in tissue regeneration and recovery of organ and tissue function. Muscle diseases affect millions of people worldwide overcome the ability of skeletal muscle to self-repair. Pro-angiogenic therapies are key in skeletal muscle regeneration where both myogenesis and angiogenesis occur. These therapies have been based on mesenchymal stem cells (MSCs), exosomes, microRNAs (miRs) and delivery of biological factors. The use of different calls of biomaterials is another approach, including ceramics, composites, and polymers. Natural polymers are use due its bioactivity and biocompatibility in addition to its use as scaffolds and in drug delivery systems. One of these polymers is the natural rubber latex (NRL) which is biocompatible, bioactive, versatile, low-costing, and capable of promoting tissue regeneration and angiogenesis. In this review, the advances in the field of pro-angiogenic therapies are discussed.
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Affiliation(s)
- Juliana Ferreira Floriano
- São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo 18.618-687, Brazil; National Heart and Lung Institute, Imperial College London, London, UK.
| | - Costanza Emanueli
- National Heart and Lung Institute, Imperial College London, London, UK
| | - Sofia Vega
- São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo 18.618-687, Brazil; Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile
| | | | | | | | | | - Joelcio Francisco Abbade
- São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo 18.618-687, Brazil
| | | | - Luis Sobrevia
- São Paulo State University (UNESP), Botucatu Medical School, Botucatu, São Paulo 18.618-687, Brazil; Cellular and Molecular Physiology Laboratory (CMPL), Department of Obstetrics, Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville E-41012, Spain; University of Queensland, Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD, 4029, Queensland, Australia; Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, 9713GZ Groningen, the Netherlands.
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19
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MacDonald A, Gross A, Jones B, Dhar M. Muscle Regeneration of the Tongue: A review of current clinical and regenerative research strategies. TISSUE ENGINEERING PART B-REVIEWS 2021; 28:1022-1034. [PMID: 34693743 DOI: 10.1089/ten.teb.2021.0133] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]
Abstract
Various abnormalities of the tongue, including cancers, commonly require surgical removal to sequester growth and metastasis. However, even minor resections can affect functional outcomes such as speech and swallowing, thereby reducing quality of life. Surgical resections alone create volumetric muscle loss whereby muscle tissue cannot self-regenerate within the tongue. In these cases, the tongue is reconstructed typically in the form of autologous skin flaps. However, flap reconstruction has many limitations and unfortunately is the primary option for oral and reconstructive surgeons to treat tongue defects. The alternative, but yet undeveloped strategy for tongue reconstruction is regenerative medicine, which widely focuses on building new organs with stem cells. Regenerative medicine has successfully treated many tissues, but research has inadequately addressed the tongue as a vital organ in need of tissue engineering. In this review, we address the current standard for tongue reconstruction, the cellular mechanisms of muscle cell development, and the stem cell studies that have attempted muscle engineering within the tongue. Until now, no review has focused on engineering the tongue with regenerative medicine, which could guide innovative strategies for tongue reconstruction.
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Affiliation(s)
- Amber MacDonald
- The University of Tennessee Knoxville College of Veterinary Medicine, 70737, Large Animal Clinical Sciences, 2407 River Drive, Knoxville, Tennessee, United States, 37996-4539;
| | - Andrew Gross
- The University of Tennessee Medical Center, 21823, Knoxville, Tennessee, United States;
| | - Brady Jones
- The University of Tennessee Medical Center, 21823, Knoxville, Tennessee, United States;
| | - Madhu Dhar
- University of Tennessee Knoxville College of Veterinary Medicine, 70737, Large Animal Clinical Sciences, College of Veterinary Medicine, 2407 River Drive, Knoxville, Tennessee, United States, 37996.,University of Tennessee;
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20
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Weng Z, Zhang B, Wu C, Yu F, Han B, Li B, Li L. Therapeutic roles of mesenchymal stem cell-derived extracellular vesicles in cancer. J Hematol Oncol 2021; 14:136. [PMID: 34479611 PMCID: PMC8414028 DOI: 10.1186/s13045-021-01141-y] [Citation(s) in RCA: 218] [Impact Index Per Article: 54.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 08/16/2021] [Indexed: 02/08/2023] Open
Abstract
Extracellular vesicles (EVs) are cell-derived membrane structures enclosing proteins, lipids, RNAs, metabolites, growth factors, and cytokines. EVs have emerged as essential intercellular communication regulators in multiple physiological and pathological processes. Previous studies revealed that mesenchymal stem cells (MSCs) could either support or suppress tumor progression in different cancers by paracrine signaling via MSC-derived EVs. Evidence suggested that MSC-derived EVs could mimic their parental cells, possessing pro-tumor and anti-tumor effects, and inherent tumor tropism. Therefore, MSC-derived EVs can be a cell-free cancer treatment alternative. This review discusses different insights regarding MSC-derived EVs' roles in cancer treatment and summarizes bioengineered MSC-derived EVs’ applications as safe and versatile anti-tumor agent delivery platforms. Meanwhile, current hurdles of moving MSC-derived EVs from bench to bedside are also discussed.
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Affiliation(s)
- Zhijie Weng
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Bowen Zhang
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Comfort Care Dental Center, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Chenzhou Wu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Fanyuan Yu
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Bo Han
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Comfort Care Dental Center, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Bo Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
| | - Longjiang Li
- State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Head and Neck Oncology, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
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21
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Wharton's Jelly-Derived Mesenchymal Stem Cells Reduce Fibrosis in a Mouse Model of Duchenne Muscular Dystrophy by Upregulating microRNA 499. Biomedicines 2021; 9:biomedicines9091089. [PMID: 34572277 PMCID: PMC8469349 DOI: 10.3390/biomedicines9091089] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2021] [Accepted: 08/23/2021] [Indexed: 01/10/2023] Open
Abstract
The aim of this study was to evaluate the therapeutic effects and mechanisms of Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) in an animal model of Duchenne muscular dystrophy (DMD). Mdx mice (3-5 months old) were administered five different doses of WJ-MSCs through their tail veins. A week after injection, grip strength measurements, creatine kinase (CK) assays, immunohistochemistry, and western blots were performed for comparison between healthy mice, mdx control mice, and WJ-MSC-injected mdx mice. WJ-MSCs exerted dose-dependent multisystem therapeutic effects in mdx mice, by decreasing CK, recovering normal behavior, regenerating muscle, and reducing apoptosis and fibrosis in skeletal muscle. We also confirmed that miR-499-5p is significantly downregulated in mdx mice, and that intravenous injection of WJ-MSCs enhanced its expression, leading to anti-fibrotic effects via targeting TGFβR 1 and 3. Thus, WJ-MSCs may represent novel allogeneic "off-the-shelf" cellular products for the treatment of DMD and possibly other muscle disorders.
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22
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Fang J, Sia J, Soto J, Wang P, Li LK, Hsueh YY, Sun R, Francis Faull K, Tidball JG, Li S. Skeletal muscle regeneration via the chemical induction and expansion of myogenic stem cells in situ or in vitro. Nat Biomed Eng 2021; 5:864-879. [PMID: 33737730 PMCID: PMC8387336 DOI: 10.1038/s41551-021-00696-y] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 02/04/2021] [Indexed: 02/05/2023]
Abstract
Muscle loss and impairment resulting from traumatic injury can be alleviated by therapies using muscle stem cells. However, collecting sufficient numbers of autologous myogenic stem cells and expanding them efficiently has been challenging. Here we show that myogenic stem cells (predominantly Pax7+ cells)-which were selectively expanded from readily obtainable dermal fibroblasts or skeletal muscle stem cells using a specific cocktail of small molecules and transplanted into muscle injuries in adult, aged or dystrophic mice-led to functional muscle regeneration in the three animal models. We also show that sustained release of the small-molecule cocktail in situ through polymer nanoparticles led to muscle repair by inducing robust activation and expansion of resident satellite cells. Chemically induced stem cell expansion in vitro and in situ may prove to be advantageous for stem cell therapies that aim to regenerate skeletal muscle and other tissues.
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Affiliation(s)
- Jun Fang
- Department of Bioengineering, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Junren Sia
- Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA
| | - Jennifer Soto
- Department of Bioengineering, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Pingping Wang
- Department of Bioengineering, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA,Beijing Key Laboratory of Bioelectromagnetism, Institute of Electrical Engineering, Chinese Academy of Sciences, Beijing 100190, China
| | - LeeAnn K. Li
- Department of Bioengineering, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA,David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90024, USA
| | - Yuan-Yu Hsueh
- Department of Bioengineering, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA,Division of Plastic Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70456, Taiwan
| | - Raymond Sun
- Department of Bioengineering, University of California, Berkeley, Berkeley, CA 94720, USA
| | - Kym Francis Faull
- Pasarow Mass Spectrometry Laboratory, Jane and Terry Semel Institute for Neuroscience and Human Behavior and Department of Psychiatry & Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - James G. Tidball
- Department of Integrative Biology and Physiology, Molecular, Cellular & Integrative Physiology Program, Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA
| | - Song Li
- Department of Bioengineering, Department of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA,Correspondence and requests for materials should be addressed to S. L.,
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23
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Hade MD, Suire CN, Suo Z. Mesenchymal Stem Cell-Derived Exosomes: Applications in Regenerative Medicine. Cells 2021; 10:1959. [PMID: 34440728 PMCID: PMC8393426 DOI: 10.3390/cells10081959] [Citation(s) in RCA: 284] [Impact Index Per Article: 71.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 07/27/2021] [Accepted: 07/30/2021] [Indexed: 12/12/2022] Open
Abstract
Exosomes are a type of extracellular vesicles, produced within multivesicular bodies, that are then released into the extracellular space through a merging of the multivesicular body with the plasma membrane. These vesicles are secreted by almost all cell types to aid in a vast array of cellular functions, including intercellular communication, cell differentiation and proliferation, angiogenesis, stress response, and immune signaling. This ability to contribute to several distinct processes is due to the complexity of exosomes, as they carry a multitude of signaling moieties, including proteins, lipids, cell surface receptors, enzymes, cytokines, transcription factors, and nucleic acids. The favorable biological properties of exosomes including biocompatibility, stability, low toxicity, and proficient exchange of molecular cargos make exosomes prime candidates for tissue engineering and regenerative medicine. Exploring the functions and molecular payloads of exosomes can facilitate tissue regeneration therapies and provide mechanistic insight into paracrine modulation of cellular activities. In this review, we summarize the current knowledge of exosome biogenesis, composition, and isolation methods. We also discuss emerging healing properties of exosomes and exosomal cargos, such as microRNAs, in brain injuries, cardiovascular disease, and COVID-19 amongst others. Overall, this review highlights the burgeoning roles and potential applications of exosomes in regenerative medicine.
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Affiliation(s)
| | | | - Zucai Suo
- Department of Biomedical Sciences, College of Medicine, Florida State University, Tallahassee, FL 32306, USA; (M.D.H.); (C.N.S.)
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24
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Abstract
Due to the ability to differentiate into variety of cell types, mesenchymal stem cells (MSCs) hold promise as source in cell-based therapy for treating injured tissue and degenerative diseases. The potential use of MSCs to replace or repair damaged tissues may depend on the efficient differentiation protocols to derive specialized cells without any negative side effects. Identification of appropriate cues that support the lineage-specific differentiation of stem cells is critical for tissue healing and cellular therapy. Recently, a number of stimuli have been utilized to direct the differentiation of stem cells. Biochemical stimuli such as small molecule, growth factor and miRNA have been traditionally used to regulate the fate of stem cells. In recent years, many studies have reported that biophysical stimuli including cyclic mechanical strain, fluid shear stress, microgravity, electrical stimulation, matrix stiffness and topography can also be sensed by stem cells through mechanical receptors, thus affecting the stem cell behaviors including their differentiation potential. In this paper, we review all the most recent literature on the application of biochemical and biophysical cues on regulating MSC differentiation. An extensive literature search was done using electronic database (Medline/Pubmed). Although there are still some challenges that need to be taken into consideration before translating these methods into clinics, biochemical and biophysical stimulation appears to be an attractive method to manipulate the lineage commitment of MSCs.
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Hassanzadeh A, Rahman HS, Markov A, Endjun JJ, Zekiy AO, Chartrand MS, Beheshtkhoo N, Kouhbanani MAJ, Marofi F, Nikoo M, Jarahian M. Mesenchymal stem/stromal cell-derived exosomes in regenerative medicine and cancer; overview of development, challenges, and opportunities. Stem Cell Res Ther 2021; 12:297. [PMID: 34020704 PMCID: PMC8138094 DOI: 10.1186/s13287-021-02378-7] [Citation(s) in RCA: 110] [Impact Index Per Article: 27.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Accepted: 05/10/2021] [Indexed: 12/13/2022] Open
Abstract
Recently, mesenchymal stem/stromal cells (MSCs) and their widespread biomedical applications have attracted great consideration from the scientific community around the world. However, reports have shown that the main populations of the transplanted MSCs are trapped in the liver, spleen, and lung upon administration, highlighting the importance of the development of cell-free therapies. Concerning rising evidence suggesting that the beneficial effects of MSC therapy are closely linked to MSC-released components, predominantly MSC-derived exosomes, the development of an MSC-based cell-free approach is of paramount importance. The exosomes are nano-sized (30100nm) lipid bilayer membrane vesicles, which are typically released by MSCs and are found in different body fluids. They include various bioactive molecules, such as messenger RNA (mRNA), microRNAs, proteins, and bioactive lipids, thus showing pronounced therapeutic competence for tissues recovery through the maintenance of their endogenous stem cells, the enhancement of regenerative phenotypic traits, inhibition of apoptosis concomitant with immune modulation, and stimulation of the angiogenesis. Conversely, the specific roles of MSC exosomes in the treatment of various tumors remain challenging. The development and clinical application of novel MSC-based cell-free strategies can be supported by better understanding their mechanisms, classifying the subpopulation of exosomes, enhancing the conditions of cell culture and isolation, and increasing the production of exosomes along with engineering exosomes to deliver drugs and therapeutic molecules to the target sites. In the current review, we deliver a brief overview of MSC-derived exosome biogenesis, composition, and isolation methods and discuss recent investigation regarding the therapeutic potential of MSC exosomes in regenerative medicine accompanied by their double-edged sword role in cancer.
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Affiliation(s)
- Ali Hassanzadeh
- Department of Applied Cell Sciences, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Heshu Sulaiman Rahman
- Department of Physiology, College of Medicine, University of Suleimanyah, Sulaymaniyah, Iraq
| | | | - Judi Januadi Endjun
- Medical Faculty, UPN Veteran, Jakarta, Indonesia.,Gatot Soebroto Indonesia Army Hospital, Jakarta, Indonesia
| | | | | | - Nasrin Beheshtkhoo
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Amin Jadidi Kouhbanani
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Faroogh Marofi
- Immunology Research Center (IRC), Tabriz University of Medical Sciences, Tabriz, Iran
| | - Marzieh Nikoo
- Department of Immunology, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Mostafa Jarahian
- Toxicology and Chemotherapy Unit (G401), German Cancer Research Center, 69120, Heidelberg, Germany.
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Nasal Turbinate Mesenchymal Stromal Cells Preserve Characteristics of Their Neural Crest Origin and Exert Distinct Paracrine Activity. J Clin Med 2021; 10:jcm10081792. [PMID: 33924095 PMCID: PMC8074274 DOI: 10.3390/jcm10081792] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 04/06/2021] [Accepted: 04/15/2021] [Indexed: 02/06/2023] Open
Abstract
The sources of mesenchymal stromal cells (MSCs) for cell therapy trials are expanding, increasing the need for their characterization. Here, we characterized multi-donor, turbinate-derived MSCs (TB-MSCs) that develop from the neural crest, and compared them to bone marrow-derived MSCs (BM-MSCs). TB-MSCs had higher proliferation potential and higher self-renewal of colony forming cells, but lower potential for multi-lineage differentiation than BM-MSCs. TB-MSCs expressed higher levels of neural crest markers and lower levels of pericyte-specific markers. These neural crest-like properties of TB-MSCs were reflected by their propensity to differentiate into neuronal cells and proliferative response to nerve growth factors. Proteomics (LC-MS/MS) analysis revealed a distinct secretome profile of TB-MSCs compared to BM and adipose tissue-derived MSCs, exhibiting enrichments of factors for cell-extracellular matrix interaction and neurogenic signaling. However, TB-MSCs and BM-MSCs exhibited comparable suppressive effects on the allo-immune response and comparable stimulatory effects on hematopoietic stem cell self-renewal. In contrast, TB-MSCs stimulated growth and metastasis of breast cancer cells more than BM-MSCs. Altogether, our multi-donor characterization of TB-MSCs reveals distinct cell autonomous and paracrine properties, reflecting their unique developmental origin. These findings support using TB-MSCs as an alternative source of MSCs with distinct biological characteristics for optimal applications in cell therapy.
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Nowzari F, Wang H, Khoradmehr A, Baghban M, Baghban N, Arandian A, Muhaddesi M, Nabipour I, Zibaii MI, Najarasl M, Taheri P, Latifi H, Tamadon A. Three-Dimensional Imaging in Stem Cell-Based Researches. Front Vet Sci 2021; 8:657525. [PMID: 33937378 PMCID: PMC8079735 DOI: 10.3389/fvets.2021.657525] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2021] [Accepted: 03/19/2021] [Indexed: 12/14/2022] Open
Abstract
Stem cells have an important role in regenerative therapies, developmental biology studies and drug screening. Basic and translational research in stem cell technology needs more detailed imaging techniques. The possibility of cell-based therapeutic strategies has been validated in the stem cell field over recent years, a more detailed characterization of the properties of stem cells is needed for connectomics of large assemblies and structural analyses of these cells. The aim of stem cell imaging is the characterization of differentiation state, cellular function, purity and cell location. Recent progress in stem cell imaging field has included ultrasound-based technique to study living stem cells and florescence microscopy-based technique to investigate stem cell three-dimensional (3D) structures. Here, we summarized the fundamental characteristics of stem cells via 3D imaging methods and also discussed the emerging literatures on 3D imaging in stem cell research and the applications of both classical 2D imaging techniques and 3D methods on stem cells biology.
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Affiliation(s)
- Fariborz Nowzari
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Huimei Wang
- Department of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Institute of Acupuncture and Moxibustion, Fudan Institutes of Integrative Medicine, Fudan University, Shanghai, China
| | - Arezoo Khoradmehr
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Mandana Baghban
- Department of Obstetrics and Gynecology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Neda Baghban
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Alireza Arandian
- Laser and Plasma Research Institute, Shahid Beheshti University, Tehran, Iran
| | - Mahdi Muhaddesi
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Iraj Nabipour
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
| | - Mohammad I. Zibaii
- Laser and Plasma Research Institute, Shahid Beheshti University, Tehran, Iran
| | - Mostafa Najarasl
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran
| | - Payam Taheri
- Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, Academic Center for Education, Culture and Research (ACECR), Tehran, Iran
| | - Hamid Latifi
- Laser and Plasma Research Institute, Shahid Beheshti University, Tehran, Iran
- Department of Physics, Shahid Beheshti University, Tehran, Iran
| | - Amin Tamadon
- The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
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Yu D, Cai Z, Li D, Zhang Y, He M, Yang Y, Liu D, Xie W, Li Y, Xiao W. Myogenic Differentiation of Stem Cells for Skeletal Muscle Regeneration. Stem Cells Int 2021; 2021:8884283. [PMID: 33628275 PMCID: PMC7884123 DOI: 10.1155/2021/8884283] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 12/22/2020] [Accepted: 01/08/2021] [Indexed: 12/11/2022] Open
Abstract
Stem cells have become a hot research topic in the field of regenerative medicine due to their self-renewal and differentiation capabilities. Skeletal muscle tissue is one of the most important tissues in the human body, and it is difficult to recover when severely damaged. However, conventional treatment methods can cause great pain to patients. Stem cell-based tissue engineering can repair skeletal muscle to the greatest extent with little damage. Therefore, the application of stem cells to skeletal muscle regeneration is very promising. In this review, we discuss scaffolds and stem cells for skeletal muscle regeneration and put forward our ideas for future development.
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Affiliation(s)
- Dengjie Yu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
| | - Zijun Cai
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
| | - Daishi Li
- Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yi Zhang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
| | - Miao He
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
| | - Yuntao Yang
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
| | - Di Liu
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
| | - Wenqing Xie
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
| | - Yusheng Li
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
| | - Wenfeng Xiao
- Department of Orthopedics, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China
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Verma YK, Verma R, Tyagi N, Behl A, Kumar S, Gangenahalli GU. COVID-19 and its Therapeutics: Special Emphasis on Mesenchymal Stem Cells Based Therapy. Stem Cell Rev Rep 2021; 17:113-131. [PMID: 32920752 PMCID: PMC7486977 DOI: 10.1007/s12015-020-10037-2] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
The novel virus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) caused the Corona Virus Disease-2019 (COVID-19) outbreak in Wuhan, Hubei province of China. This virus disseminated rapidly and reached to an unprecedented pandemic proportion in more than 213 nations with a large number of fatalities. The hypersecretion of pro-inflammatory cytokines is the main cause of mortality and morbidity due to COVID-19, therefore strategies that avert the cytokine storm may play a crucial role in abating the severity of COVID-19. This review highlights the minute details of SARS-CoV-2, its genomic organization, genomic variations within structural and non-structural proteins and viral progression mechanism in human beings. The approaches like antiviral strategies are discussed, including drugs that obstruct viral propagation and suppress the pro-inflammatory cytokines. This compilation emphasizes Mesenchymal Stem Cells (MSCs) based therapy alone or in combination with other therapeutics as an attractive curative approach for COVID-19 pandemic. The MSCs and its secretome, including antimicrobial peptides (AMPs) have various capabilities, for instance, immunomodulation, regeneration, antimicrobial properties, potential for attenuating the cytokine storm and bare minimum chances of being infected with SARS-CoV-2 virus. The immunomodulatory property of MSCs affects inflammatory state and regulates immune response during SARS-CoV-2 infection. However, as of now, there is no WHO-approved MSCs based therapy for the treatment of COVID-19 infection. Graphical abstract.
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Affiliation(s)
- Yogesh Kumar Verma
- Division of Stem Cell & Gene Therapy Research, Institute of Nuclear Medicine & Allied Sciences (INMAS), Brig. S.K. Mazumdar Road, Delhi, 110054, India
| | - Ranjan Verma
- Division of Stem Cell & Gene Therapy Research, Institute of Nuclear Medicine & Allied Sciences (INMAS), Brig. S.K. Mazumdar Road, Delhi, 110054, India
| | - Nishant Tyagi
- Division of Stem Cell & Gene Therapy Research, Institute of Nuclear Medicine & Allied Sciences (INMAS), Brig. S.K. Mazumdar Road, Delhi, 110054, India
| | - Amanpreet Behl
- Division of Stem Cell & Gene Therapy Research, Institute of Nuclear Medicine & Allied Sciences (INMAS), Brig. S.K. Mazumdar Road, Delhi, 110054, India
| | - Subodh Kumar
- Division of Stem Cell & Gene Therapy Research, Institute of Nuclear Medicine & Allied Sciences (INMAS), Brig. S.K. Mazumdar Road, Delhi, 110054, India
| | - Gurudutta U Gangenahalli
- Division of Stem Cell & Gene Therapy Research, Institute of Nuclear Medicine & Allied Sciences (INMAS), Brig. S.K. Mazumdar Road, Delhi, 110054, India.
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Effect of 20(S)-Hydroxycholesterol on Multilineage Differentiation of Mesenchymal Stem Cells Isolated from Compact Bones in Chicken. Genes (Basel) 2020; 11:genes11111360. [PMID: 33213081 PMCID: PMC7698591 DOI: 10.3390/genes11111360] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2020] [Revised: 11/11/2020] [Accepted: 11/12/2020] [Indexed: 11/17/2022] Open
Abstract
Bone health and body weight gain have significant economic and welfare importance in the poultry industry. Mesenchymal stem cells (MSCs) are common progenitors of different cell lineages such as osteoblasts, adipocytes, and myocytes. Specific oxysterols have shown to be pro-osteogenic and anti-adipogenic in mouse and human MSCs. To determine the effect of 20(S)-hydroxycholesterol (20S) on osteogenic, adipogenic, and myogenic differentiation in chicken, mesenchymal stem cells isolated from compact bones of broiler chickens (cBMSCs) were subjected to various doses of 20S, and markers of lineage-specific mRNA were analyzed using real-time PCR and cell cytochemistry. Further studies were conducted to evaluate the molecular mechanisms involved in lineage-specific differentiation pathways. Like human and mouse MSCs, 20S oxysterol expressed pro-osteogenic, pro-myogenic, and anti-adipogenic differentiation potential in cBMSCs. Moreover, 20(S)-Hydroxycholesterol induced markers of osteogenic genes and myogenic regulatory factors when exposed to cBMSCs treated with their specific medium. In contrast, 20S oxysterol suppressed expression of adipogenic marker genes when exposed to cBMSCs treated with OA, an adipogenic precursor of cBMSCs. To elucidate the molecular mechanism by which 20S exerts its differentiation potential in all three lineages, we focused on the hedgehog signaling pathway. The hedgehog inhibitor, cyclopamine, completely reversed the effect of 20S induced expression of osteogenic and anti-adipogenic mRNA. However, there was no change in the mRNA expression of myogenic genes. The results showed that 20S oxysterol promotes osteogenic and myogenic differentiation and decreases adipocyte differentiation of cBMSCs. This study also showed that the induction of osteogenesis and adipogenesis inhibition in cBMSCs by 20S is mediated through the hedgehog signaling mechanism. The results indicated that 20(S) could play an important role in the differentiation of chicken-derived MSCs and provided the theory basis on developing an intervention strategy to regulate skeletal, myogenic, and adipogenic differentiation in chicken, which will contribute to improving chicken bone health and meat quality. The current results provide the rationale for the further study of regulatory mechanisms of bioactive molecules on the differentiation of MSCs in chicken, which can help to address skeletal health problems in poultry.
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Mishra S, Sevak JK, Das A, Arimbasseri GA, Bhatnagar S, Gopinath SD. Umbilical cord tissue is a robust source for mesenchymal stem cells with enhanced myogenic differentiation potential compared to cord blood. Sci Rep 2020; 10:18978. [PMID: 33149204 PMCID: PMC7642376 DOI: 10.1038/s41598-020-75102-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Accepted: 10/12/2020] [Indexed: 02/02/2023] Open
Abstract
Differentiation of mesenchymal stem cells (MSCs) derived from two different sources of fetal tissues such as umbilical cord blood (UCB) and tissue (UCT) into skeletal muscle have remained underexplored. Here, we present a comparative analysis of UCB and UCT MSCs, in terms of surface markers, proliferation and senescence marker expression. We find that CD45-CD34- MSCs obtained from UCT and UCB of term births display differences in the combinatorial expression of key MSC markers CD105 and CD90. Importantly, UCT MSCs display greater yield, higher purity, shorter culture time, and lower rates of senescence in culture compared to UCB MSCs. Using a robust myogenic differentiation protocol, we show that UCT MSCs differentiate more robustly into muscle than UCB MSCs by transcriptomic sequencing and specific myogenic markers. Functional assays reveal that CD90, and not CD105 expression promotes myogenic differentiation in MSCs and could explain the enhanced myogenic potential of UCT MSCs. These results suggest that in comparison to large volumes of UCB that are routinely used to obtain MSCs and with limited success, UCT is a more reliable, robust, and convenient source of MSCs to derive cells of the myogenic lineage for both therapeutic purposes and increasing our understanding of developmental processes.
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Affiliation(s)
- Shivangi Mishra
- Pediatric Biology Center, Translational Health Science and Technology Institute (THSTI), NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, PO Box #04, Faridabad, 121001, India
| | - Jayesh Kumar Sevak
- Pediatric Biology Center, Translational Health Science and Technology Institute (THSTI), NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, PO Box #04, Faridabad, 121001, India
| | - Anamica Das
- National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India
| | | | - Shinjini Bhatnagar
- Pediatric Biology Center, Translational Health Science and Technology Institute (THSTI), NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, PO Box #04, Faridabad, 121001, India
| | - Suchitra D Gopinath
- Pediatric Biology Center, Translational Health Science and Technology Institute (THSTI), NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, PO Box #04, Faridabad, 121001, India.
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Bajetto A, Thellung S, Dellacasagrande I, Pagano A, Barbieri F, Florio T. Cross talk between mesenchymal and glioblastoma stem cells: Communication beyond controversies. Stem Cells Transl Med 2020; 9:1310-1330. [PMID: 32543030 PMCID: PMC7581451 DOI: 10.1002/sctm.20-0161] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 05/25/2020] [Accepted: 05/30/2020] [Indexed: 12/12/2022] Open
Abstract
Mesenchymal stem cells (MSCs) can be isolated from bone marrow or other adult tissues (adipose tissue, dental pulp, amniotic fluid, and umbilical cord). In vitro, MSCs grow as adherent cells, display fibroblast-like morphology, and self-renew, undergoing specific mesodermal differentiation. High heterogeneity of MSCs from different origin, and differences in preparation techniques, make difficult to uniform their functional properties for therapeutic purposes. Immunomodulatory, migratory, and differentiation ability, fueled clinical MSC application in regenerative medicine, whereas beneficial effects are currently mainly ascribed to their secretome and extracellular vesicles. MSC translational potential in cancer therapy exploits putative anti-tumor activity and inherent tropism toward tumor sites to deliver cytotoxic drugs. However, controversial results emerged evaluating either the therapeutic potential or homing efficiency of MSCs, as both antitumor and protumor effects were reported. Glioblastoma (GBM) is the most malignant brain tumor and its development and aggressive nature is sustained by cancer stem cells (CSCs) and the identification of effective therapeutic is required. MSC dualistic action, tumor-promoting or tumor-targeting, is dependent on secreted factors and extracellular vesicles driving a complex cross talk between MSCs and GBM CSCs. Tumor-tropic ability of MSCs, besides providing an alternative therapeutic approach, could represent a tool to understand the biology of GBM CSCs and related paracrine mechanisms, underpinning MSC-GBM interactions. In this review, recent findings on the complex nature of MSCs will be highlighted, focusing on their elusive impact on GBM progression and aggressiveness by direct cell-cell interaction and via secretome, also facing the perspectives and challenges in treatment strategies.
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Affiliation(s)
- Adriana Bajetto
- Dipartimento di Medicina InternaUniversità di GenovaGenovaItaly
| | | | | | - Aldo Pagano
- Dipartimento di Medicina SperimentaleUniversità di GenovaGenovaItaly
- IRCCS Ospedale Policlinico San MartinoGenovaItaly
| | | | - Tullio Florio
- Dipartimento di Medicina InternaUniversità di GenovaGenovaItaly
- IRCCS Ospedale Policlinico San MartinoGenovaItaly
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Lee EJ, Jain M, Alimperti S. Bone Microvasculature: Stimulus for Tissue Function and Regeneration. TISSUE ENGINEERING PART B-REVIEWS 2020; 27:313-329. [PMID: 32940150 DOI: 10.1089/ten.teb.2020.0154] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Bone is a highly vascularized organ, providing structural support to the body, and its development, regeneration, and remodeling depend on the microvascular homeostasis. Loss or impairment of vascular function can develop diseases, such as large bone defects, avascular necrosis, osteoporosis, osteoarthritis, and osteopetrosis. In this review, we summarize how vasculature controls bone development and homeostasis in normal and disease cases. A better understanding of this process will facilitate the development of novel disease treatments that promote bone regeneration and remodeling. Specifically, approaches based on tissue engineering components, such as stem cells and growth factors, have demonstrated the capacity to induce bone microvasculature regeneration and mineralization. This knowledge will have relevant clinical implications for the treatment of bone disorders by developing novel pharmaceutical approaches and bone grafts. Finally, the tissue engineering approaches incorporating vascular components may widely be applied to treat other organ diseases by enhancing their regeneration capacity. Impact statement Bone vasculature is imperative in the process of bone development, regeneration, and remodeling. Alterations or disruption of the bone vasculature leads to loss of bone homeostasis and the development of bone diseases. In this study, we review the role of vasculature on bone diseases and how vascular tissue engineering strategies, with a detailed emphasis on the role of stem cells and growth factors, will contribute to bone therapeutics.
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Affiliation(s)
- Eun-Jin Lee
- American Dental Association Science and Research Institute, Gaithersburg, Maryland, USA
| | - Mahim Jain
- Kennedy Krieger Institute, John Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Stella Alimperti
- American Dental Association Science and Research Institute, Gaithersburg, Maryland, USA
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Sheveleva ON, Payushina OV, Butorina NN, Domaratskaya EI. The Myogenic Potential of Mesenchymal Stromal Cells and Their Effect on Skeletal Muscle Regeneration. BIOL BULL+ 2020. [DOI: 10.1134/s106235902005009x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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35
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Prats-Puig A, García-Retortillo S, Puig-Parnau M, Vasileva F, Font-Lladó R, Xargay-Torrent S, Carreras-Badosa G, Mas-Parés B, Bassols J, López-Bermejo A. DNA Methylation Reorganization of Skeletal Muscle-Specific Genes in Response to Gestational Obesity. Front Physiol 2020; 11:938. [PMID: 32848869 PMCID: PMC7412435 DOI: 10.3389/fphys.2020.00938] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 07/13/2020] [Indexed: 12/25/2022] Open
Abstract
The goals were to investigate in umbilical cord tissue if gestational obesity: (1) was associated with changes in DNA methylation of skeletal muscle-specific genes; (2) could modulate the co-methylation interactions among these genes. Additionally, we assessed the associations between DNA methylation levels and infant's variables at birth and at age 6. DNA methylation was measured in sixteen pregnant women [8-gestational obesity group; 8-control group] in umbilical cord using the Infinium Methylation EPIC Bead Chip microarray. Differentially methylated CpGs were identified with Beta Regression Models [false discovery rate (FDR) < 0.05 and an Odds Ratio > 1.5 or < 0.67]. DNA methylation interactions between CpGs of skeletal muscle-specific genes were studied using data from Pearson correlation matrices. In order to quantify the interactions within each network, the number of links was computed. This identification analysis reported 38 differential methylated CpGs within skeletal muscle-specific genes (comprising 4 categories: contractibility, structure, myokines, and myogenesis). Compared to control group, gestational obesity (1) promotes hypermethylation in highly methylated genes and hypomethylation in low methylated genes; (2) CpGs in regions close to transcription sites and with high CpG density are hypomethylated while regions distant to transcriptions sites and with low CpG density are hypermethylated; (3) diminishes the number of total interactions in the co-methylation network. Interestingly, the associations between infant's fasting glucose at age 6 and MYL6, MYH11, TNNT3, TPM2, CXCL2, and NCAM1 were still relevant after correcting for multiple testing. In conclusion, our study showed a complex interaction between gestational obesity and the epigenetic status of muscle-specific genes in umbilical cord tissue. Additionally, gestational obesity may alter the functional co-methylation connectivity of CpG within skeletal muscle-specific genes interactions, our results revealing an extensive reorganization of methylation in response to maternal overweight. Finally, changes in methylation levels of skeletal muscle specific genes may have persistent effects on the offspring of mothers with gestational obesity.
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Affiliation(s)
- Anna Prats-Puig
- University School of Health and Sport (EUSES), University of Girona, Girona, Spain
| | - Sergi García-Retortillo
- University School of Health and Sport (EUSES), University of Girona, Girona, Spain
- Complex Systems in Sport, National Institute of Physical Education and Sport of Catalonia (INEFC), Universitat de Barcelona (UB), Barcelona, Spain
| | - Miquel Puig-Parnau
- University School of Health and Sport (EUSES), University of Girona, Girona, Spain
| | - Fidanka Vasileva
- Faculty of Physical Education, Sport and Health, Ss. Cyril and Methodius University, Skopje, North Macedonia
| | - Raquel Font-Lladó
- University School of Health and Sport (EUSES), University of Girona, Girona, Spain
| | - Sílvia Xargay-Torrent
- Pediatric Endocrinology, Girona Institute for Biomedical Research, Dr. Josep Trueta Hospital, Girona, Spain
| | - Gemma Carreras-Badosa
- Pediatric Endocrinology, Girona Institute for Biomedical Research, Dr. Josep Trueta Hospital, Girona, Spain
| | - Berta Mas-Parés
- Maternal & Fetal Metabolic Research, Girona Institute for Biomedical Research, Salt, Spain
| | - Judit Bassols
- Maternal & Fetal Metabolic Research, Girona Institute for Biomedical Research, Salt, Spain
| | - Abel López-Bermejo
- Pediatric Endocrinology, Girona Institute for Biomedical Research, Dr. Josep Trueta Hospital, Girona, Spain
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Yang JH, Liu FX, Wang JH, Cheng M, Wang SF, Xu DH. Mesenchymal stem cells and mesenchymal stem cell-derived extracellular vesicles: Potential roles in rheumatic diseases. World J Stem Cells 2020; 12:688-705. [PMID: 32843922 PMCID: PMC7415241 DOI: 10.4252/wjsc.v12.i7.688] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 05/26/2020] [Accepted: 06/10/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) have been widely investigated in rheumatic disease due to their immunomodulatory and regenerative properties. Recently, mounting studies have implicated the therapeutic potency of MSCs mostly due to the bioactive factors they produce. Extracellular vesicles (EVs) derived from MSCs have been identified as a promising cell-free therapy due to low immunogenicity. Rheumatic disease, primarily including rheumatoid arthritis and osteoarthritis, is a group of diseases in which immune dysregulation and chronic progressive inflammation lead to irreversible joint damage. Targeting MSCs and MSC-derived EVs may be a more effective and promising therapeutic strategy for rheumatic diseases.
AIM To evaluate the potential therapeutic effectiveness of MSCs and EVs generated from MSCs in rheumatic diseases.
METHODS PubMed was searched for the relevant literature using corresponding search terms alone or in combination. Papers published in English language from January 1999 to February 2020 were considered. Preliminary screening of papers concerning analysis of "immunomodulatory function" or "regenerative function" by scrutinizing the titles and abstracts of the literature, excluded the papers not related to the subject of the article. Some other related studies were obtained by manually retrieving the reference lists of papers that comply with the selection criteria, and these studies were screened to meet the final selection and exclusion criteria.
RESULTS Eighty-six papers were ultimately selected for analysis. After analysis of the literature, it was found that both MSCs and EVs generated from MSCs have great potential in multiple rheumatic diseases, such as rheumatoid arthritis and osteoarthritis, in repair and regeneration of tissues, inhibition of inflammatory response, and regulation of body immunity via promoting chondrogenesis, regulating innate and adaptive immune cells, and regulating the secretion of inflammatory factors. But EVs from MSCs exhibit much more advantages over MSCs, which may represent another promising cell-free restorative strategy. Targeting MSCs and MSC-derived EVs may be a more efficient treatment for patients with rheumatic diseases.
CONCLUSION The enormous potential of MSCs and EVs from MSCs in immunomodulation and tissue regeneration offers a new idea for the treatment of rheumatism. However, more in-depth exploration is needed before their clinical application.
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Affiliation(s)
- Jing-Han Yang
- Central Laboratory of the First Affiliated Hospital, Weifang Medical University, Weifang 261000, Shandong Province, China
- Department of Rheumatology of the First Affiliated Hospital, Weifang Medical University, Weifang 261000, Shandong Province, China
| | - Feng-Xia Liu
- Department of Allergy, Weifang People’s Hospital, Weifang 261000, Shandong Province, China
| | - Jing-Hua Wang
- Central Laboratory of the First Affiliated Hospital, Weifang Medical University, Weifang 261000, Shandong Province, China
- Department of Rheumatology of the First Affiliated Hospital, Weifang Medical University, Weifang 261000, Shandong Province, China
| | - Min Cheng
- Department of Physiology, Weifang Medical University, Weifang 261000, Shandong Province, China
| | - Shu-Feng Wang
- Medical Experimental Training Center, Weifang Medical University, Weifang 261000, Shandong Province, China
| | - Dong-Hua Xu
- Central Laboratory of the First Affiliated Hospital, Weifang Medical University, Weifang 261000, Shandong Province, China
- Department of Rheumatology of the First Affiliated Hospital, Weifang Medical University, Weifang 261000, Shandong Province, China
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Comparative Analysis of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells between Preeclampsia and Normal Pregnant Women. Stem Cells Int 2020; 2020:8403192. [PMID: 32587622 PMCID: PMC7298345 DOI: 10.1155/2020/8403192] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 03/03/2020] [Accepted: 03/26/2020] [Indexed: 12/26/2022] Open
Abstract
Preeclampsia is a syndrome characterized by deterioration of either the maternal condition or the fetal condition. The adverse intrauterine environment made by preeclampsia results into intrauterine growth restriction and increased risk of a variety of diseases in future life. Given the adverse environment of fetal circulation made in the preeclamptic condition, and the role of mesenchymal stem cell (MSC) as a multipotent progenitor cell, we hypothesized that MSCs derived from human umbilical cord blood (hUCB-MSCs) obtained from preeclampsia are adversely altered or affected compared with normal pregnancy. The aim of this study was to analyze the biological characteristics and compare the functional abilities and gene expression patterns of hUCB-MSCs originating from pregnant women with and without severe preeclampsia. hUCB-MSCs were isolated and cultured from 28 pregnant women with severe preeclampsia and 30 normal pregnant women. hUCB-MSCs obtained from women with preeclampsia were less proliferative and more senescent and had lower telomerase activity and higher ROS activity than cells from women with normal pregnancy. In addition, many senescence-related differentially expressed genes (DEGs) were identified by analysis of microarray gene expression profiles and significantly associated with the Gene Ontology term cell aging. In conclusion, hUCB-MSCs obtained from women with preeclampsia showed the poorly proliferative, more senescent, and decreased telomerase activity, and these characters may be related with functional impairment of MSC from preeclampsia compared with cells from normal pregnancy.
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Floriano JF, Willis G, Catapano F, de Lima PR, Reis FVDS, Barbosa AMP, Rudge MVC, Emanueli C. Exosomes Could Offer New Options to Combat the Long-Term Complications Inflicted by Gestational Diabetes Mellitus. Cells 2020; 9:E675. [PMID: 32164322 PMCID: PMC7140615 DOI: 10.3390/cells9030675] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2020] [Revised: 02/20/2020] [Accepted: 02/29/2020] [Indexed: 02/08/2023] Open
Abstract
Gestational diabetes Mellitus (GDM) is a complex clinical condition that promotes pelvic floor myopathy, thus predisposing sufferers to urinary incontinence (UI). GDM usually regresses after birth. Nonetheless, a GDM history is associated with higher risk of subsequently developing type 2 diabetes, cardiovascular diseases (CVD) and UI. Some aspects of the pathophysiology of GDM remain unclear and the associated pathologies (outcomes) are poorly addressed, simultaneously raising public health costs and diminishing women's quality of life. Exosomes are small extracellular vesicles produced and actively secreted by cells as part of their intercellular communication system. Exosomes are heterogenous in their cargo and depending on the cell sources and environment, they can mediate both pathogenetic and therapeutic functions. With the advancement in knowledge of exosomes, new perspectives have emerged to support the mechanistic understanding, prediction/diagnosis and ultimately, treatment of the post-GMD outcomes. Here, we will review recent advances in knowledge of the role of exosomes in GDM and related areas and discuss the possibilities for translating exosomes as therapeutic agents in the GDM clinical setting.
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Affiliation(s)
- Juliana Ferreira Floriano
- Botucatu Medical School, Sao Paulo State University, 18618687 Botucatu, Brazil; (J.F.F.); (P.R.d.L.); (F.V.D.S.R.); (A.M.P.B.)
| | - Gareth Willis
- Division of Newborn Medicine/Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - Francesco Catapano
- National Heart and Lung Institute, Imperial College London, London W12 0NN, UK;
| | - Patrícia Rodrigues de Lima
- Botucatu Medical School, Sao Paulo State University, 18618687 Botucatu, Brazil; (J.F.F.); (P.R.d.L.); (F.V.D.S.R.); (A.M.P.B.)
| | | | - Angélica Mercia Pascon Barbosa
- Botucatu Medical School, Sao Paulo State University, 18618687 Botucatu, Brazil; (J.F.F.); (P.R.d.L.); (F.V.D.S.R.); (A.M.P.B.)
| | - Marilza Vieira Cunha Rudge
- Botucatu Medical School, Sao Paulo State University, 18618687 Botucatu, Brazil; (J.F.F.); (P.R.d.L.); (F.V.D.S.R.); (A.M.P.B.)
| | - Costanza Emanueli
- National Heart and Lung Institute, Imperial College London, London W12 0NN, UK;
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Park M, Nepali S, Lew H. Isolation and Characterization of Extraocular Muscle-Derived Muscle Progenitor Cells from Normal and Graves' Orbitopathy Patients. Stem Cells Dev 2020; 29:353-363. [PMID: 31969085 DOI: 10.1089/scd.2019.0212] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Mesenchymal stem cells (MSCs) are useful for various purposes, including tissue engineering, regeneration, and gene therapy. MSCs isolated from extraocular muscles (EOMs) can be easily expanded in vitro, and can undergo multilineage differentiations involving adipogenesis, chondrogenesis, osteogenesis, and even neuronal or myogenic differentiation. This study aimed to isolate, characterize, and compare extraocular muscle-derived muscle progenitor cells (EOM-MPCs) from normal subjects and patients with Graves' orbitopathy (GO). EOM was obtained during strabismus surgery. Flow cytometry was conducted to identify CD surface antigens such as CD34, CD45, CD44, CD59, CD73, and CD90. We quantitated various cytokines secreted from MSCs, including interleukin (IL)-1α, IL-2, IL-6, IL-8, IL-10, IL-12, IL17A, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ, using a multi-analysis enzyme-linked immunosorbent assay array kit. We performed Oil Red O staining for adipogenesis, Alzarin Red staining for osteogenesis, Alcian blue staining for chondrogenesis, and polymerase chain reaction to measure messenger RNA expression during myogenesis. Our results show that EOM-MPCs from normal subjects and GO patients had similar levels of surface antigen expression and cytokine secretion. There was also no significant difference in the multilineage differentiation of adipocytes, chondrocytes, osteocytes, and myoblasts from EOM-MPCs taken from normal subjects and GO patients. However, hyaluronic acid synthetase 2 expression was higher after induction with tafluprost in EOM-MPCs from GO patients when compared with normal subjects. Together, these results show that EOM-MPCs derived from normal subjects are a good source for stem cell-based therapy for various disorders.
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Affiliation(s)
- Mira Park
- Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
| | - Sarmila Nepali
- Department of Ophthalmology, University of Miami, Coral Gables, Florida
| | - Helen Lew
- Department of Ophthalmology, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea
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Barisic D, Erb M, Follo M, Al-Mudaris D, Rolauffs B, Hart ML. Lack of a skeletal muscle phenotype in adult human bone marrow stromal cells following xenogeneic-free expansion. Stem Cell Res Ther 2020; 11:79. [PMID: 32087752 PMCID: PMC7036219 DOI: 10.1186/s13287-020-1587-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 01/22/2020] [Accepted: 02/05/2020] [Indexed: 02/07/2023] Open
Abstract
Background Many studies have elegantly shown that murine and rat bone marrow-derived mesenchymal stromal cells (bmMSCs) contribute to muscle regeneration and improve muscle function. Yet, the ability of transplanted human bmMSCs to manifest myogenic potential shows conflicting results. While human adipose- and umbilical cord-derived MSCs can be differentiated into a skeletal muscle phenotype using horse serum (HS), bmMSCs have only been shown to differentiate towards the skeletal muscle lineage using a complex mixture of cytokines followed by transfection with notch intracellular domain. Methods Since xenogeneic-free growth supplements are increasingly being used in the expansion of bmMSCs in clinical trials, we investigated the effects of human plasma and platelet lysate (P/PL) on the expression of neuromuscular markers and whether P/PL-expanded human bmMSCs could be differentiated towards a skeletal myogenic phenotype. Neuromuscular markers were measured using the highly sensitive droplet digital polymerase chain reaction for measuring the expression of Myf5, MyoD, MyoG, ACTA1, Desmin, GAP-43, and Coronin 1b transcripts, by performing immunofluorescence for the expression of Desmin, GAP-43, and MEF2, and flow cytometry for the expression of CD56/neural cell adhesion molecule (NCAM). Results Despite that bmMSCs expressed the myogenic regulatory factor (MRF) MEF2 after expansion in P/PL, bmMSCs cultured under such conditions did not express other essential MRFs including Myf5, MyoD, MyoG, or ACTA1 needed for myogenesis. Moreover, HS did not induce myogenesis of bmMSCs and hence did not induce the expression of any of these myogenic markers. P/PL, however, did lead to a significant increase in neurogenic GAP-43, as well as Desmin expression, and resulted in a high baseline expression of the neurogenic gene Coronin 1b which was sustained under further P/PL or HS culture conditions. Fetal bovine serum resulted in equally high levels of GAP-43 and Coronin 1b. Moreover, the proportion of CD56/NCAM-positive bmMSCs cultured in P/PL was 5.9 ± 2.1. Conclusions These data suggest that P/PL may prime a small portion of bmMSCs towards an early neural precursor cell type. Collectively, this shows that P/PL partially primes the cells towards a neurogenic phenotype, but does not prime adult human bmMSCs towards the skeletal muscle lineage.
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Affiliation(s)
- Dominik Barisic
- G.E.R.N. Center for Tissue Replacement, Regeneration and Neogenesis, Department of Orthopaedics and Trauma Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Marita Erb
- G.E.R.N. Center for Tissue Replacement, Regeneration and Neogenesis, Department of Orthopaedics and Trauma Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Marie Follo
- Department of Medicine I, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Dahlia Al-Mudaris
- G.E.R.N. Center for Tissue Replacement, Regeneration and Neogenesis, Department of Orthopaedics and Trauma Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Bernd Rolauffs
- G.E.R.N. Center for Tissue Replacement, Regeneration and Neogenesis, Department of Orthopaedics and Trauma Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
| | - Melanie L Hart
- G.E.R.N. Center for Tissue Replacement, Regeneration and Neogenesis, Department of Orthopaedics and Trauma Surgery, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
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Kasprzycka P, Archacka K, Kowalski K, Mierzejewski B, Zimowska M, Grabowska I, Piotrowski M, Rafałko M, Ryżko A, Irhashava A, Senderowski K, Gołąbek M, Stremińska W, Jańczyk-Ilach K, Koblowska M, Iwanicka-Nowicka R, Fogtman A, Janowski M, Walczak P, Ciemerych MA, Brzoska E. The factors present in regenerating muscles impact bone marrow-derived mesenchymal stromal/stem cell fusion with myoblasts. Stem Cell Res Ther 2019; 10:343. [PMID: 31753006 PMCID: PMC6873517 DOI: 10.1186/s13287-019-1444-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Revised: 09/23/2019] [Accepted: 10/04/2019] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Satellite cells, a population of unipotent stem cells attached to muscle fibers, determine the excellent regenerative capability of injured skeletal muscles. Myogenic potential is also exhibited by other cell populations, which exist in the skeletal muscles or come from other niches. Mesenchymal stromal/stem cells inhabiting the bone marrow do not spontaneously differentiate into muscle cells, but there is some evidence that they are capable to follow the myogenic program and/or fuse with myoblasts. METHODS In the present study we analyzed whether IGF-1, IL-4, IL-6, and SDF-1 could impact human and porcine bone marrow-derived mesenchymal stromal/stem cells (hBM-MSCs and pBM-MSCs) and induce expression of myogenic regulatory factors, skeletal muscle-specific structural, and adhesion proteins. Moreover, we investigated whether these factors could induce both types of BM-MSCs to fuse with myoblasts. IGF-1, IL-4, IL-6, and SDF-1 were selected on the basis of their role in embryonic myogenesis as well as skeletal muscle regeneration. RESULTS We found that hBM-MSCs and pBM-MSCs cultured in vitro in the presence of IGF-1, IL-4, IL-6, or SDF-1 did not upregulate myogenic regulatory factors. Consequently, we confirmed the lack of their naïve myogenic potential. However, we noticed that IL-4 and IL-6 impacted proliferation and IL-4, IL-6, and SDF-1 improved migration of hBM-MSCs. IL-4 treatment resulted in the significant increase in the level of mRNA encoding CD9, NCAM, VCAM, and m-cadherin, i.e., proteins engaged in cell fusion during myotube formation. Additionally, the CD9 expression level was also driven by IGF-1 treatment. Furthermore, the pre-treatment of hBM-MSCs either with IGF-1, IL-4, or SDF-1 and treatment of pBM-MSCs either with IGF-1 or IL-4 increased the efficacy of hybrid myotube formation between these cells and C2C12 myoblasts. CONCLUSIONS To conclude, our study revealed that treatment with IGF-1, IL-4, IL-6, or SDF-1 affects BM-MSC interaction with myoblasts; however, it does not directly promote myogenic differentiation of these cells.
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Affiliation(s)
- Paulina Kasprzycka
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Karolina Archacka
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Kamil Kowalski
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Bartosz Mierzejewski
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Małgorzata Zimowska
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Iwona Grabowska
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Mariusz Piotrowski
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Milena Rafałko
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Agata Ryżko
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Aliksandra Irhashava
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Kamil Senderowski
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Magdalena Gołąbek
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Władysława Stremińska
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Katarzyna Jańczyk-Ilach
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Marta Koblowska
- Laboratory of Systems Biology, Faculty of Biology, University of Warsaw, Pawinskiego 5a St, 02-106 Warsaw, Poland
| | - Roksana Iwanicka-Nowicka
- Laboratory of Systems Biology, Faculty of Biology, University of Warsaw, Pawinskiego 5a St, 02-106 Warsaw, Poland
- Laboratory of Microarray Analysis, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a St, 02-106 Warsaw, Poland
| | - Anna Fogtman
- Laboratory of Microarray Analysis, Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawinskiego 5a St, 02-106 Warsaw, Poland
| | - Mirosław Janowski
- Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA
- Cellular Imaging Section and Vascular Biology Program, Institute for Cell Engineering, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA
- NeuroRepair Department, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawinskiego 5 St, 02-106 Warsaw, Poland
| | - Piotr Walczak
- Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA
- Department of Neurosurgery, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-719 Olsztyn, Poland
- Institute for Cell Engineering, Cellular Imaging Section, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA
| | - Maria A. Ciemerych
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
| | - Edyta Brzoska
- Department of Cytology, Faculty of Biology, University of Warsaw, Miecznikowa 1 St, 02-096 Warsaw, Poland
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Xu B, Zhang M, Perlingeiro RCR, Shen W. Skeletal Muscle Constructs Engineered from Human Embryonic Stem Cell Derived Myogenic Progenitors Exhibit Enhanced Contractile Forces When Differentiated in a Medium Containing EGM‐2 Supplements. ACTA ACUST UNITED AC 2019; 3:e1900005. [DOI: 10.1002/adbi.201900005] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 10/08/2019] [Indexed: 12/22/2022]
Affiliation(s)
- Bin Xu
- Department of Biomedical Engineering University of Minnesota Minneapolis MN 55455 USA
| | - Mengen Zhang
- Department of Biomedical Engineering University of Minnesota Minneapolis MN 55455 USA
| | - Rita C. R. Perlingeiro
- Department of Medicine University of Minnesota Minneapolis MN 55455 USA
- Stem Cell Institute and Institute for Engineering in Medicine University of Minnesota Minneapolis Minnesota 55455 USA
| | - Wei Shen
- Department of Biomedical Engineering University of Minnesota Minneapolis MN 55455 USA
- Stem Cell Institute and Institute for Engineering in Medicine University of Minnesota Minneapolis Minnesota 55455 USA
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Gois Beghini D, Iwao Horita S, Monteiro da Fonseca Cardoso L, Anastacio Alves L, Nagaraju K, Henriques-Pons A. A Promising Future for Stem-Cell-Based Therapies in Muscular Dystrophies-In Vitro and In Vivo Treatments to Boost Cellular Engraftment. Int J Mol Sci 2019; 20:ijms20215433. [PMID: 31683627 PMCID: PMC6861917 DOI: 10.3390/ijms20215433] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2019] [Revised: 08/28/2019] [Accepted: 09/23/2019] [Indexed: 02/06/2023] Open
Abstract
Muscular dystrophies (MD) are a group of genetic diseases that lead to skeletal muscle wasting and may affect many organs (multisystem). Unfortunately, no curative therapies are available at present for MD patients, and current treatments mainly address the symptoms. Thus, stem-cell-based therapies may present hope for improvement of life quality and expectancy. Different stem cell types lead to skeletal muscle regeneration and they have potential to be used for cellular therapies, although with several limitations. In this review, we propose a combination of genetic, biochemical, and cell culture treatments to correct pathogenic genetic alterations and to increase proliferation, dispersion, fusion, and differentiation into new or hybrid myotubes. These boosted stem cells can also be injected into pretreate recipient muscles to improve engraftment. We believe that this combination of treatments targeting the limitations of stem-cell-based therapies may result in safer and more efficient therapies for MD patients. Matricryptins have also discussed.
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Affiliation(s)
- Daniela Gois Beghini
- Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro (RJ) 21040-900, Brazil.
| | - Samuel Iwao Horita
- Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro (RJ) 21040-900, Brazil.
| | | | - Luiz Anastacio Alves
- Laboratório de Comunicação Celular, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro (RJ) 21040-900, Brazil.
| | - Kanneboyina Nagaraju
- Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, Binghamton University, New York, NY 13902, USA.
| | - Andrea Henriques-Pons
- Laboratório de Inovações em Terapias, Ensino e Bioprodutos, Instituto Oswaldo Cruz, Fiocruz, Rio de Janeiro (RJ) 21040-900, Brazil.
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Eukaryotic initiation factor 3, subunit C silencing inhibits cell proliferation and promotes apoptosis in human ovarian cancer cells. Biosci Rep 2019; 39:BSR20191124. [PMID: 31316002 PMCID: PMC6685053 DOI: 10.1042/bsr20191124] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Revised: 07/02/2019] [Accepted: 07/14/2019] [Indexed: 01/23/2023] Open
Abstract
Ovarian cancer remains the leading cause of death among all gynaecological cancers, illustrating the urgent need to understand the molecular mechanisms involved in this disease. Eukaryotic initiation factor 3c (EIF3c) plays an important role in protein translation and cancer cell growth and proliferation, but its role in human ovarian cancer is unclear. Our results showed that EIF3c silencing significantly up-regulated 217 and down-regulated 340 genes. Ingenuity Pathway Analysis (IPA) indicated that the top differentially expressed genes are involved in ‘Classical Pathways’, ‘Diseases and Functions’ and ‘Networks’, especially those involved in signalling and cellular growth and proliferation. In addition, eIF3c silencing inhibited cellular proliferation, enhanced apoptosis and regulated the expression of apoptosis-associated proteins. In conclusion, these results indicate that by dysregulating translational initiation, eIF3c plays an important role in the proliferation and survival of human ovarian cancer cells. These results should provide experimental directions for further in-depth studies on important human ovarian cancer cell pathways.
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Miao S, Nowicki M, Cui H, Lee SJ, Zhou X, Mills DK, Zhang LG. 4D anisotropic skeletal muscle tissue constructs fabricated by staircase effect strategy. Biofabrication 2019; 11:035030. [PMID: 31026857 PMCID: PMC6746184 DOI: 10.1088/1758-5090/ab1d07] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Like the morphology of native tissue fiber arrangement (such as skeletal muscle), unidirectional anisotropic scaffolds are highly desired as a means to guide cell behavior in anisotropic tissue engineering. In contrast, contour-like staircases exhibit directional topographical cues and are judged as an inevitable defect of fused deposition modeling (FDM). In this study, we will translate this staircase defect into an effective bioengineering strategy by integrating FDM with surface coating technique (FCT) to investigate the effect of topographical cues on regulating behaviors of human mesenchymal stem cells (hMSCs) toward skeletal muscle tissues. This integrated approach serves to fabricate shape-specific, multiple dimensional, anisotropic scaffolds using different biomaterials. 2D anisotropic scaffolds, first demonstrated with different polycaprolactone concentrations herein, efficiently direct hMSC alignment, especially when the scaffold is immobilized on a support ring. By surface coating the polymer solution inside FDM-printed sacrificial structures, 3D anisotropic scaffolds with thin wall features are developed and used to regulate seeded hMSCs through a self-established rotating bioreactor. Using layer-by-layer coating, along with a shape memory polymer, smart constructs exhibiting shape fix and recovery processes are prepared, bringing this study into the realm of 4D printing. Immunofluorescence staining and real-time quantitative polymerase chain reaction analysis confirm that the topographical cues created via FCT significantly enhance the expression of myogenic genes, including myoblast differentiation protein-1, desmin, and myosin heavy chain-2. We conclude that there are broad application potentials for this FCT strategy in tissue engineering as many tissues and organs, including skeletal muscle, possess highly organized and anisotropic extracellular matrix components.
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Affiliation(s)
- Shida Miao
- Department of Aerospace and Mechanical Engineering, The George Washington University, 800 22nd St, NW Washington DC 20052, United States of America
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Schreurs M, Suttorp CM, Mutsaers HAM, Kuijpers-Jagtman AM, Von den Hoff JW, Ongkosuwito EM, Carvajal Monroy PL, Wagener FADTG. Tissue engineering strategies combining molecular targets against inflammation and fibrosis, and umbilical cord blood stem cells to improve hampered muscle and skin regeneration following cleft repair. Med Res Rev 2019; 40:9-26. [PMID: 31104334 PMCID: PMC6972684 DOI: 10.1002/med.21594] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Revised: 04/17/2019] [Accepted: 04/19/2019] [Indexed: 12/18/2022]
Abstract
Cleft lip with or without cleft palate is a congenital deformity that occurs in about 1 of 700 newborns, affecting the dentition, bone, skin, muscles and mucosa in the orofacial region. A cleft can give rise to problems with maxillofacial growth, dental development, speech, and eating, and can also cause hearing impairment. Surgical repair of the lip may lead to impaired regeneration of muscle and skin, fibrosis, and scar formation. This may result in hampered facial growth and dental development affecting oral function and lip and nose esthetics. Therefore, secondary surgery to correct the scar is often indicated. We will discuss the molecular and cellular pathways involved in facial and lip myogenesis, muscle anatomy in the normal and cleft lip, and complications following surgery. The aim of this review is to outline a novel molecular and cellular strategy to improve musculature and skin regeneration and to reduce scar formation following cleft repair. Orofacial clefting can be diagnosed in the fetus through prenatal ultrasound screening and allows planning for the harvesting of umbilical cord blood stem cells upon birth. Tissue engineering techniques using these cord blood stem cells and molecular targeting of inflammation and fibrosis during surgery may promote tissue regeneration. We expect that this novel strategy improves both muscle and skin regeneration, resulting in better function and esthetics after cleft repair.
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Affiliation(s)
- Michaël Schreurs
- Department of Dentistry, Section of Orthodontics and Craniofacial Biology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - C Maarten Suttorp
- Department of Dentistry, Section of Orthodontics and Craniofacial Biology, Radboud University Medical Centre, Nijmegen, The Netherlands.,Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands
| | | | | | - Johannes W Von den Hoff
- Department of Dentistry, Section of Orthodontics and Craniofacial Biology, Radboud University Medical Centre, Nijmegen, The Netherlands.,Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Edwin M Ongkosuwito
- Department of Dentistry, Section of Orthodontics and Craniofacial Biology, Radboud University Medical Centre, Nijmegen, The Netherlands
| | - Paola L Carvajal Monroy
- Department of Oral & Maxillofacial Surgery, Special Dental Care and Orthodontics, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Frank A D T G Wagener
- Department of Dentistry, Section of Orthodontics and Craniofacial Biology, Radboud University Medical Centre, Nijmegen, The Netherlands.,Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Nijmegen, The Netherlands
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47
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Tang X, Daneshmandi L, Awale G, Nair LS, Laurencin CT. Skeletal Muscle Regenerative Engineering. REGENERATIVE ENGINEERING AND TRANSLATIONAL MEDICINE 2019; 5:233-251. [PMID: 33778155 DOI: 10.1007/s40883-019-00102-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Skeletal muscles have the intrinsic ability to regenerate after minor injury, but under certain circumstances such as severe trauma from accidents, chronic diseases or battlefield injuries the regeneration process is limited. Skeletal muscle regenerative engineering has emerged as a promising approach to address this clinical issue. The regenerative engineering approach involves the convergence of advanced materials science, stem cell science, physical forces, insights from developmental biology, and clinical translation. This article reviews recent studies showing the potential of the convergences of technologies involving biomaterials, stem cells and bioactive factors in concert with clinical translation, in promoting skeletal muscle regeneration. Several types of biomaterials such as electrospun nanofibers, hydrogels, patterned scaffolds, decellularized tissues, and conductive matrices are being investigated. Detailed discussions are given on how these biomaterials can interact with cells and modulate their behavior through physical, chemical and mechanical cues. In addition, the application of physical forces such as mechanical and electrical stimulation are reviewed as strategies that can further enhance muscle contractility and functionality. The review also discusses established animal models to evaluate regeneration in two clinically relevant muscle injuries; volumetric muscle loss (VML) and muscle atrophy upon rotator cuff injury. Regenerative engineering approaches using advanced biomaterials, cells, and physical forces, developmental cues along with insights from immunology, genetics and other aspects of clinical translation hold significant potential to develop promising strategies to support skeletal muscle regeneration.
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Affiliation(s)
- Xiaoyan Tang
- Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA.,Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA.,Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA.,Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA
| | - Leila Daneshmandi
- Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA.,Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA.,Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA.,Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA
| | - Guleid Awale
- Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA.,Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA.,Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA.,Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA
| | - Lakshmi S Nair
- Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA.,Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA.,Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA.,Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA.,Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA
| | - Cato T Laurencin
- Connecticut Convergence Institute for Translation in Regenerative Engineering, UConn Health, Farmington, CT 06030, USA.,Department of Orthopaedic Surgery, UConn Health, Farmington, CT 06030, USA.,Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, UConn Health, Farmington, CT 06030, USA.,Department of Materials Science and Engineering, University of Connecticut, Storrs, CT 06269, USA.,Department of Biomedical Engineering, University of Connecticut, Storrs, CT 06269, USA.,Department of Chemical and Biomolecular Engineering, University of Connecticut, Storrs, CT 06269, USA
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48
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Shen C, Yang C, Xu S, Zhao H. Comparison of osteogenic differentiation capacity in mesenchymal stem cells derived from human amniotic membrane (AM), umbilical cord (UC), chorionic membrane (CM), and decidua (DC). Cell Biosci 2019; 9:17. [PMID: 30792848 PMCID: PMC6371545 DOI: 10.1186/s13578-019-0281-3] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2018] [Accepted: 02/04/2019] [Indexed: 02/09/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) have been extensively explored as a promising therapeutic agent in the field of bone tissue engineering due to their osteogenic differentiation ability. In this study, the osteogenic differential ability and the effect of fibronectin and laminin on the osteogenic differentiation in four types of MSCs derived from placental tissue are compared to determine the ideal source for bone reconstruction tissue engineering. RESULTS The present study examines the osteogenic differentiation levels of four types of MSCs using alizarin red staining and quantifies the calcium levels and alkaline phosphatase (ALP) activity. In addition, this study examines the osteoblast differentiation protein markers osterix, collagen I, osteopontin, and osteocalcin using a Western blot assay. qPCR and EdU labeling assays were employed to identify the kinetics of osteogenic differentiation. Calcium deposit levels, ALP activity, and osteopontin and osteocalcin concentrations were determined to confirm the role of Extracellular matrix (ECM) components role on the osteogenic differentiation of MSCs. The data demonstrated that MSCs isolated from different layers of placenta had different potentials to differentiate into osteogenic cells. Importantly, AM-MSCs and UC-MSCs differentiated into the osteoblast stage more efficiently and quickly than CM-MSCs and DC-MSCs, which was associated with a decrease in their proliferation ability. Among the different types of MSCs, AM-MSCs and UC-MSCs had a higher osteogenic differentiation potential induced by fibronectin due to enhanced phosphorylation during the Akt and ERK pathways. CONCLUSIONS Taken together, these results indicate that AM-MSCs and UC-MSCs possess a higher osteogenic potential, and fibronectin can robustly enhance the osteogenic potential of the Akt and ERK pathways.
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Affiliation(s)
- Chongyang Shen
- Basic Medicine School, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Chuan Yang
- Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of the Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of China
| | - Shijun Xu
- College Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, People’s Republic of China
| | - Hai Zhao
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, People’s Republic of China
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49
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Adhikari R, Chen C, Waters E, West FD, Kim WK. Isolation and Differentiation of Mesenchymal Stem Cells From Broiler Chicken Compact Bones. Front Physiol 2019; 9:1892. [PMID: 30723419 PMCID: PMC6350342 DOI: 10.3389/fphys.2018.01892] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2018] [Accepted: 12/14/2018] [Indexed: 12/17/2022] Open
Abstract
Chicken mesenchymal stem cells (MSCs) can be used as an avian culture model to better understand osteogenic, adipogenic, and myogenic pathways and to identify unique bioactive nutrients and molecules which can promote or inhibit these pathways. MSCs could also be used as a model to study various developmental, physiological, and therapeutic processes in avian and other species. MSCs are multipotent stem cells that are capable of differentiation into bone, muscle, fat, and closely related lineages and express unique and specific cell surface markers. MSCs have been isolated from numerous sources including human, mouse, rabbit, and chicken with potential clinical and agricultural applications. MSCs from chicken compact bones have not been isolated and characterized yet. In this study, MSCs were isolated from compact bones of the femur and tibia of day-old male broiler chicks to investigate the biological characteristics of the isolated cells. Isolated cells took 8–10 days to expand, demonstrated a monolayer growth pattern and were plastic adherent. Putative MSCs were spindle-shaped with elongated ends and showed rapid proliferation. MSCs demonstrated osteoblastic, adipocytic, and myogenic differentiation when induced with specific differentiation media. Cell surface markers for MSCs such as CD90, CD105, CD73, CD44 were detected positive and CD31, CD34, and CD45 cells were detected negative by PCR assay. The results suggest that MSCs isolated from broiler compact bones (cBMSCs) possess similar biological characteristics as MSCs isolated from other chicken tissue sources.
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Affiliation(s)
- Roshan Adhikari
- Department of Poultry Science, University of Georgia, Athens, GA, United States.,Regenerative Bioscience Center, University of Georgia, Athens, GA, United States
| | - Chongxiao Chen
- Department of Poultry Science, University of Georgia, Athens, GA, United States.,Regenerative Bioscience Center, University of Georgia, Athens, GA, United States
| | - Elizabeth Waters
- Regenerative Bioscience Center, University of Georgia, Athens, GA, United States.,Department of Animal and Dairy Science, University of Georgia, Athens, GA, United States
| | - Franklin D West
- Regenerative Bioscience Center, University of Georgia, Athens, GA, United States.,Department of Animal and Dairy Science, University of Georgia, Athens, GA, United States
| | - Woo Kyun Kim
- Department of Poultry Science, University of Georgia, Athens, GA, United States.,Regenerative Bioscience Center, University of Georgia, Athens, GA, United States
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50
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Pan D, Chang X, Xu M, Zhang M, Zhang S, Wang Y, Luo X, Xu J, Yang X, Sun X. UMSC-derived exosomes promote retinal ganglion cells survival in a rat model of optic nerve crush. J Chem Neuroanat 2019; 96:134-139. [PMID: 30639447 DOI: 10.1016/j.jchemneu.2019.01.006] [Citation(s) in RCA: 64] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2018] [Revised: 12/12/2018] [Accepted: 01/09/2019] [Indexed: 12/17/2022]
Abstract
Traumatic optic neuropathy or glaucoma lead to retinal ganglion cells loss and cause blindness, and there is no effective therapy strategy by far. Mesenchymal cells from the Wharton's jelly of the umbilical cord (umbilical cord mesenchymal stem cells, UMSCs) and UMSC-derived exosomes (UMSC-Exos) are promising candidates for allogeneic therapy in regenerative medicine, but their effort on optic nerve injury and the underlying mechanism remains undefined. In the present study, we investigated the functions of UMSC-Exos in a rat optic nerve crush (ONC) model. After three times of treatments with an interval of one week, we found that the UMSC-Exos significantly promoted Brn3a+ retinal ganglion cells (RGCs) survival in retinal ganglion cell layer compared with PBS controls. UMSC-Exos also significantly promoted GFAP+ glia cells activation in retina and optic nerve. However, no increase of GAP43+ axon counts in the optic nerve was found after UMSC-Exos treatment. Thus, our results demonstrate that UMSC-derived exosomes may play a role in neuroprotection by promoting the RGCs survival and glia cells activation but not the axon regeneration.
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Affiliation(s)
- Dongyan Pan
- Department of Ophthalmology, Changhai Hospital, Second Military Medical University School of Medicine, Shanghai, China; Department of Anatomy, Second Military Medical University School of Medicine, Shanghai, China; Department of Histology and Embryology, Second Military Medical University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Cell Engineering, Shanghai, China
| | - Xin Chang
- Department of Histology and Embryology, Second Military Medical University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Cell Engineering, Shanghai, China
| | - Mengqiao Xu
- Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
| | - Mingke Zhang
- Department of Histology and Embryology, Second Military Medical University School of Medicine, Shanghai, China
| | - Shoumei Zhang
- Department of Anatomy, Second Military Medical University School of Medicine, Shanghai, China
| | - Yue Wang
- Department of Histology and Embryology, Second Military Medical University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Cell Engineering, Shanghai, China
| | - Xueting Luo
- Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China.
| | - Jiajun Xu
- Department of Anatomy, Second Military Medical University School of Medicine, Shanghai, China.
| | - Xiangqun Yang
- Department of Anatomy, Second Military Medical University School of Medicine, Shanghai, China.
| | - Xiaodong Sun
- Department of Ophthalmology, Shanghai General Hospital (Shanghai First People's Hospital), Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Fundus Diseases, Shanghai, China; Shanghai Engineering Center for Visual Science and Photomedicine, Shanghai, China
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