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For: Otsuru S, Desbourdes L, Guess AJ, Hofmann TJ, Relation T, Kaito T, Dominici M, Iwamoto M, Horwitz EM. Extracellular vesicles released from mesenchymal stromal cells stimulate bone growth in osteogenesis imperfecta. Cytotherapy 2017;20:62-73. [PMID: 29107738 DOI: 10.1016/j.jcyt.2017.09.012] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Revised: 09/14/2017] [Accepted: 09/15/2017] [Indexed: 01/01/2023]

For:	Otsuru S, Desbourdes L, Guess AJ, Hofmann TJ, Relation T, Kaito T, Dominici M, Iwamoto M, Horwitz EM. Extracellular vesicles released from mesenchymal stromal cells stimulate bone growth in osteogenesis imperfecta. Cytotherapy 2017;20:62-73. [PMID: 29107738 DOI: 10.1016/j.jcyt.2017.09.012] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2017] [Revised: 09/14/2017] [Accepted: 09/15/2017] [Indexed: 01/01/2023]

Number

Cited by Other Article(s)

Hetta HF, Elsaghir A, Sijercic VC, Ahmed AK, Gad SA, Zeleke MS, Alanazi FE, Ramadan YN. Clinical Progress in Mesenchymal Stem Cell Therapy: A Focus on Rheumatic Diseases. Immun Inflamm Dis 2025;13:e70189. [PMID: 40353645 PMCID: PMC12067559 DOI: 10.1002/iid3.70189] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 05/10/2024] [Accepted: 03/21/2025] [Indexed: 05/14/2025] Open

Abstract

BACKGROUND

Rheumatic diseases are chronic immune-mediated disorders affecting multiple organ systems and significantly impairing patients' quality of life. Current treatments primarily provide symptomatic relief without offering a cure. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their ability to differentiate into various cell types and their immunomodulatory, anti-inflammatory, and regenerative properties. This review aims to summarize the clinical progress of MSC therapy in rheumatic diseases, highlight key findings from preclinical and clinical studies, and discuss challenges and future directions.

METHODOLOGY

A comprehensive review of preclinical and clinical studies on MSC therapy in rheumatic diseases, including systemic lupus erythematosus, rheumatoid arthritis, ankylosing spondylitis, osteoarthritis, osteoporosis, Sjögren's syndrome, Crohn's disease, fibromyalgia, systemic sclerosis, dermatomyositis, and polymyositis, was conducted. Emerging strategies to enhance MSC efficacy and overcome current limitations were also analyzed.

RESULTS AND DISCUSSION

Evidence from preclinical and clinical studies suggests that MSC therapy can reduce inflammation, modulate immune responses, and promote tissue repair in various rheumatic diseases. Clinical trials have demonstrated potential benefits, including symptom relief and disease progression delay. However, challenges such as variability in treatment response, optimal cell source and dosing, long-term safety concerns, and regulatory hurdles remain significant barriers to clinical translation. Standardized protocols and further research are required to optimize MSC application.

CONCLUSION

MSC therapy holds promise for managing rheumatic diseases, offering potential disease-modifying effects beyond conventional treatments. However, large-scale, well-controlled clinical trials are essential to establish efficacy, safety, and long-term therapeutic potential. Addressing current limitations through optimized treatment protocols and regulatory frameworks will be key to its successful integration into clinical practice.

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He X, Chu XY, Chen X, Xiang YL, Li ZL, Gao CY, Luan YY, Yang K, Zhang DL. Dental pulp stem cell‑derived extracellular vesicles loaded with hydrogels promote osteogenesis in rats with alveolar bone defects. Mol Med Rep 2025;31:29. [PMID: 39540371 PMCID: PMC11582518 DOI: 10.3892/mmr.2024.13393] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 09/30/2024] [Indexed: 11/16/2024] Open

Abstract

Alveolar bone defects caused by inflammation, trauma and tumors adversely affect periodontal health, causing tooth loosening or dentition defects, thus affecting denture or implant repair. Advancements in tissue engineering technology and stem cell biology have significantly improved the regenerative reconstruction of alveolar bone defects. The multiple trophic activities of extracellular vesicles (EVs) produced by mesenchymal stem cells play important roles in exerting their therapeutic effects. Several studies have reported the role of dental pulp stem cells (DPSCs) in bone regeneration, but the regenerative effects of DPSC‑EVs on alveolar bone defects are unclear. In the present study, the osteogenic effects of DPSC‑EVs on Hertwig's epithelial root sheath (HERS) cells in vitro and their osteoinductive effects in an alveolar bone defect rat model were investigated. The results showed that DPSC‑EVs significantly promoted the expression of osteogenic genes, such as runt‑related transcription factor 2 and alkaline phosphatase, and increased the osteogenic differentiation capability of HERS. These findings suggested that transforming growth factor β1 inhibition decreased DPSC‑EV‑induced Smad, MAPK and ERK phosphorylation in HERS. In vivo, DPSC‑EV‑loaded hydrogels were transplanted into the alveolar sockets of Sprague‑Dawley rats and observed for eight weeks. The new bone grew concentrically in the DPSC‑EV or DPSC‑EV‑loaded hydrogel group, with greater bone mass than that in the control group, and the bone volume/total volume increased notably. The results confirmed the osteogenic and osteoinductive effects of DPSC‑EVs and DPSC‑Exo‑loaded hydrogels on alveolar bone defects. Due to their low immunogenicity, high stability, good biocompatibility and osteogenic propensity, DPSC‑EV‑loaded hydrogels are a safe cell‑free therapeutic approach for defective alveolar bone regeneration.

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Dubois N, Van Morckhoven D, Tilleman L, Van Nieuwerburgh F, Bron D, Lagneaux L, Stamatopoulos B. Extracellular vesicles from chronic lymphocytic leukemia cells promote leukemia aggressiveness by inducing the differentiation of monocytes into nurse-like cells via an RNA-dependent mechanism. Hemasphere 2025;9:e70068. [PMID: 39822586 PMCID: PMC11735956 DOI: 10.1002/hem3.70068] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2024] [Revised: 10/25/2024] [Accepted: 11/07/2024] [Indexed: 01/19/2025] Open

Guo Q, Zhai Q, Ji P. The Role of Mitochondrial Homeostasis in Mesenchymal Stem Cell Therapy-Potential Implications in the Treatment of Osteogenesis Imperfecta. Pharmaceuticals (Basel) 2024;17:1297. [PMID: 39458939 PMCID: PMC11510265 DOI: 10.3390/ph17101297] [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: 06/20/2024] [Revised: 09/11/2024] [Accepted: 09/18/2024] [Indexed: 10/28/2024] Open

Ochieng BO, Zhao L, Ye Z. Three-Dimensional Bioprinting in Vascular Tissue Engineering and Tissue Vascularization of Cardiovascular Diseases. TISSUE ENGINEERING. PART B, REVIEWS 2024;30:340-358. [PMID: 37885200 DOI: 10.1089/ten.teb.2023.0175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/28/2023]

Mello DB, Mesquita FCP, Silva dos Santos D, Asensi KD, Dias ML, Campos de Carvalho AC, Goldenberg RCDS, Kasai-Brunswick TH. Mesenchymal Stromal Cell-Based Products: Challenges and Clinical Therapeutic Options. Int J Mol Sci 2024;25:6063. [PMID: 38892249 PMCID: PMC11173248 DOI: 10.3390/ijms25116063] [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: 05/02/2024] [Revised: 05/24/2024] [Accepted: 05/26/2024] [Indexed: 06/21/2024] Open

Affiliation(s)

Debora B. Mello National Center of Structural Biology and Bioimaging, CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; (D.B.M.); (A.C.C.d.C.)
Fernanda Cristina Paccola Mesquita Regenerative Medicine Research Department, The Texas Heart Institute, Houston, TX 77030, USA;
Danúbia Silva dos Santos Center of Cellular Technology, National Institute of Cardiology, INC, Rio de Janeiro 22240-002, Brazil; National Institute of Science and Technology for Regenerative Medicine-REGENERA, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; (K.D.A.); (R.C.d.S.G.)
Karina Dutra Asensi National Institute of Science and Technology for Regenerative Medicine-REGENERA, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; (K.D.A.); (R.C.d.S.G.) Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil;
Marlon Lemos Dias Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil;
Antonio Carlos Campos de Carvalho National Center of Structural Biology and Bioimaging, CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; (D.B.M.); (A.C.C.d.C.) National Institute of Science and Technology for Regenerative Medicine-REGENERA, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; (K.D.A.); (R.C.d.S.G.) Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil;
Regina Coeli dos Santos Goldenberg National Institute of Science and Technology for Regenerative Medicine-REGENERA, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; (K.D.A.); (R.C.d.S.G.) Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil;
Tais Hanae Kasai-Brunswick National Center of Structural Biology and Bioimaging, CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; (D.B.M.); (A.C.C.d.C.) National Institute of Science and Technology for Regenerative Medicine-REGENERA, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil; (K.D.A.); (R.C.d.S.G.) Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro 21941-902, Brazil;

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Chen X, Yang N, Li B, Gao X, Wang Y, Wang Q, Liu X, Zhang Z, Zhang R. Visualization Analysis of Small Extracellular Vesicles in the Application of Bone-Related Diseases. Cells 2024;13:904. [PMID: 38891036 PMCID: PMC11171653 DOI: 10.3390/cells13110904] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2024] [Revised: 05/17/2024] [Accepted: 05/20/2024] [Indexed: 06/20/2024] Open

Affiliation(s)

Xinjiani Chen Department of Biotechnology and Biomedicine, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China; (X.C.); (N.Y.); (B.L.); (X.G.); (Y.W.); (Q.W.); (X.L.) Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
Ning Yang Department of Biotechnology and Biomedicine, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China; (X.C.); (N.Y.); (B.L.); (X.G.); (Y.W.); (Q.W.); (X.L.)
Bailei Li Department of Biotechnology and Biomedicine, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China; (X.C.); (N.Y.); (B.L.); (X.G.); (Y.W.); (Q.W.); (X.L.) Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
Xinyu Gao Department of Biotechnology and Biomedicine, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China; (X.C.); (N.Y.); (B.L.); (X.G.); (Y.W.); (Q.W.); (X.L.)
Yayu Wang Department of Biotechnology and Biomedicine, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China; (X.C.); (N.Y.); (B.L.); (X.G.); (Y.W.); (Q.W.); (X.L.) Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
Qin Wang Department of Biotechnology and Biomedicine, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China; (X.C.); (N.Y.); (B.L.); (X.G.); (Y.W.); (Q.W.); (X.L.) Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China
Xiaojun Liu Department of Biotechnology and Biomedicine, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China; (X.C.); (N.Y.); (B.L.); (X.G.); (Y.W.); (Q.W.); (X.L.) Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, 705 Yatai Road, Jiaxing 314006, China Taizhou Innovation Center, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 318000, China
Zhen Zhang Department of Biotechnology and Biomedicine, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China; (X.C.); (N.Y.); (B.L.); (X.G.); (Y.W.); (Q.W.); (X.L.) Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, 705 Yatai Road, Jiaxing 314006, China
Rongqing Zhang Department of Biotechnology and Biomedicine, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, China; (X.C.); (N.Y.); (B.L.); (X.G.); (Y.W.); (Q.W.); (X.L.) Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, 705 Yatai Road, Jiaxing 314006, China Taizhou Innovation Center, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 318000, China

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Gençer EB, Lor YK, Abomaray F, El Andaloussi S, Pernemalm M, Sharma N, Hagey DW, Görgens A, Gustafsson MO, Le Blanc K, Asad Toonsi M, Walther-Jallow L, Götherström C. Transcriptomic and proteomic profiles of fetal versus adult mesenchymal stromal cells and mesenchymal stromal cell-derived extracellular vesicles. Stem Cell Res Ther 2024;15:77. [PMID: 38475970 DOI: 10.1186/s13287-024-03683-7] [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: 11/08/2023] [Accepted: 02/23/2024] [Indexed: 03/14/2024] Open

Abstract

BACKGROUND

Mesenchymal stem/stromal cells (MSCs) can regenerate tissues through engraftment and differentiation but also via paracrine signalling via extracellular vesicles (EVs). Fetal-derived MSCs (fMSCs) have been shown, both in vitro and in animal studies, to be more efficient than adult MSC (aMSCs) in generating bone and muscle but the underlying reason for this difference has not yet been clearly elucidated. In this study, we aimed to systematically investigate the differences between fetal and adult MSCs and MSC-derived EVs at the phenotypic, RNA, and protein levels.

METHODS

We carried out a detailed and comparative characterization of culture-expanded fetal liver derived MSCs (fMSCs) and adult bone marrow derived MSCs (aMSCs) phenotypically, and the MSCs and MSC-derived EVs were analysed using transcriptomics and proteomics approaches with RNA Sequencing and Mass Spectrometry.

RESULTS

Fetal MSCs were smaller, exhibited increased proliferation and colony-forming capacity, delayed onset of senescence, and demonstrated superior osteoblast differentiation capability compared to their adult counterparts. Gene Ontology analysis revealed that fMSCs displayed upregulated gene sets such as "Positive regulation of stem cell populations", "Maintenance of stemness" and "Muscle cell development/contraction/Myogenesis" in comparison to aMSCs. Conversely, aMSCs displayed upregulated gene sets such as "Complement cascade", "Adipogenesis", "Extracellular matrix glycoproteins" and "Cellular metabolism", and on the protein level, "Epithelial cell differentiation" pathways. Signalling entropy analysis suggested that fMSCs exhibit higher signalling promiscuity and hence, higher potency than aMSCs. Gene ontology comparisons revealed that fetal MSC-derived EVs (fEVs) were enriched for "Collagen fibril organization", "Protein folding", and "Response to transforming growth factor beta" compared to adult MSC-derived EVs (aEVs), whereas no significant difference in protein expression in aEVs compared to fEVs could be detected.

CONCLUSIONS

This study provides detailed and systematic insight into the differences between fMSCs and aMSCs, and MSC-derived EVs. The key finding across phenotypic, transcriptomic and proteomic levels is that fMSCs exhibit higher potency than aMSCs, meaning they are in a more undifferentiated state. Additionally, fMSCs and fMSC-derived EVs may possess greater bone forming capacity compared to aMSCs. Therefore, using fMSCs may lead to better treatment efficacy, especially in musculoskeletal diseases.

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Affiliation(s)

Emine Begüm Gençer Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Yuk Kit Lor Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Fawaz Abomaray Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Samir El Andaloussi Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden
Maria Pernemalm Cancer Proteomics Mass Spectrometry, Science for Life Laboratory, Department of Oncology- Pathology, Karolinska Institutet, Stockholm, Sweden
Nidhi Sharma Cancer Proteomics Mass Spectrometry, Science for Life Laboratory, Department of Oncology- Pathology, Karolinska Institutet, Stockholm, Sweden
Daniel W Hagey Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden
André Görgens Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, Essen, Germany
Manuela O Gustafsson Biomolecular Medicine, Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden
Katarina Le Blanc Department of Cellular Therapy and Allogeneic Stem Cell Transplantation (CAST), Karolinska University Hospital Huddinge and Karolinska Comprehensive Cancer Center, Stockholm, Sweden Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet, Stockholm, Sweden
Mawaddah Asad Toonsi Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden Department of Pediatrics, College of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
Lilian Walther-Jallow Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
Cecilia Götherström Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

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Miron RJ, Estrin NE, Sculean A, Zhang Y. Understanding exosomes: Part 2-Emerging leaders in regenerative medicine. Periodontol 2000 2024;94:257-414. [PMID: 38591622 DOI: 10.1111/prd.12561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2024] [Revised: 02/16/2024] [Accepted: 02/21/2024] [Indexed: 04/10/2024]

Nataliya B, Mikhail A, Vladimir P, Olga G, Maksim V, Ivan Z, Ekaterina N, Georgy S, Natalia D, Pavel M, Andrey C, Maria S, Maxim K, Anastasiya T, Uliana D, Zhanna A, Vsevolod T, Natalia K, Anastasiya E. Mesenchymal stromal cells facilitate resolution of pulmonary fibrosis by miR-29c and miR-129 intercellular transfer. Exp Mol Med 2023;55:1399-1412. [PMID: 37394579 PMCID: PMC10393964 DOI: 10.1038/s12276-023-01017-w] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 03/14/2023] [Accepted: 03/26/2023] [Indexed: 07/04/2023] Open

Affiliation(s)

Basalova Nataliya Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation.
Arbatskiy Mikhail Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation
Popov Vladimir Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation
Grigorieva Olga Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation
Vigovskiy Maksim Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation
Zaytsev Ivan Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation
Novoseletskaya Ekaterina Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation
Sagaradze Georgy Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation
Danilova Natalia Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation Department of Clinical Pathology, Medical Research and Education Centre, Lomonosov Moscow State University, Moscow, Russian Federation
Malkov Pavel Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation Department of Clinical Pathology, Medical Research and Education Centre, Lomonosov Moscow State University, Moscow, Russian Federation
Cherniaev Andrey Division of Fundamental Medicine of Federal State Budgetary Institution "Pulmonology Scientific Research Institute under Federal Medical and Biological Agency of Russian Federation", Moscow, Russian Federation Research Institute of Human Morphology, Moscow, Russian Federation
Samsonova Maria Division of Fundamental Medicine of Federal State Budgetary Institution "Pulmonology Scientific Research Institute under Federal Medical and Biological Agency of Russian Federation", Moscow, Russian Federation Research Institute of Human Morphology, Moscow, Russian Federation
Karagyaur Maxim Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation
Tolstoluzhinskaya Anastasiya Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation
Dyachkova Uliana Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation
Akopyan Zhanna Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation
Tkachuk Vsevolod Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation
Kalinina Natalia Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation
Efimenko Anastasiya Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, Moscow, Russian Federation Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation

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Tavasolian F, Inman RD. Biology and therapeutic potential of mesenchymal stem cell extracellular vesicles in axial spondyloarthritis. Commun Biol 2023;6:413. [PMID: 37059822 PMCID: PMC10104809 DOI: 10.1038/s42003-023-04743-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 03/21/2023] [Indexed: 04/16/2023] Open

Ren S, Lin Y, Liu W, Yang L, Zhao M. MSC-Exos: Important active factor of bone regeneration. Front Bioeng Biotechnol 2023;11:1136453. [PMID: 36814713 PMCID: PMC9939647 DOI: 10.3389/fbioe.2023.1136453] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Accepted: 01/24/2023] [Indexed: 02/08/2023] Open

Lang E, Semon JA. Mesenchymal stem cells in the treatment of osteogenesis imperfecta. CELL REGENERATION (LONDON, ENGLAND) 2023;12:7. [PMID: 36725748 PMCID: PMC9892307 DOI: 10.1186/s13619-022-00146-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/17/2022] [Accepted: 10/18/2022] [Indexed: 02/03/2023]

Burns JS, Kassem M. Identifying Biomarkers for Osteogenic Potency Assay Development. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2023;1420:39-58. [PMID: 37258783 DOI: 10.1007/978-3-031-30040-0_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]

Bowles-Welch AC, Jimenez AC, Stevens HY, Frey Rubio DA, Kippner LE, Yeago C, Roy K. Mesenchymal stromal cells for bone trauma, defects, and disease: Considerations for manufacturing, clinical translation, and effective treatments. Bone Rep 2023. [DOI: 10.1016/j.bonr.2023.101656] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023] Open

Alcorta-Sevillano N, Infante A, Macías I, Rodríguez CI. Murine Animal Models in Osteogenesis Imperfecta: The Quest for Improving the Quality of Life. Int J Mol Sci 2022;24:ijms24010184. [PMID: 36613624 PMCID: PMC9820162 DOI: 10.3390/ijms24010184] [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: 11/24/2022] [Revised: 12/16/2022] [Accepted: 12/19/2022] [Indexed: 12/25/2022] Open

de Almeida Fuzeta M, Gonçalves PP, Fernandes-Platzgummer A, Cabral JMS, Bernardes N, da Silva CL. From Promise to Reality: Bioengineering Strategies to Enhance the Therapeutic Potential of Extracellular Vesicles. Bioengineering (Basel) 2022;9:675. [PMID: 36354586 PMCID: PMC9687169 DOI: 10.3390/bioengineering9110675] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2022] [Revised: 10/31/2022] [Accepted: 11/03/2022] [Indexed: 11/13/2022] Open

Affiliation(s)

Miguel de Almeida Fuzeta iBB–Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal Associate Laboratory i4HB–Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
Pedro P. Gonçalves iBB–Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal Associate Laboratory i4HB–Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
Ana Fernandes-Platzgummer iBB–Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal Associate Laboratory i4HB–Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
Joaquim M. S. Cabral iBB–Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal Associate Laboratory i4HB–Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
Nuno Bernardes iBB–Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal Associate Laboratory i4HB–Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
Cláudia L. da Silva iBB–Institute for Bioengineering and Biosciences and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal Associate Laboratory i4HB–Institute for Health and Bioeconomy at Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal

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Arévalo‐Turrubiarte M, Baratta M, Ponti G, Chiaradia E, Martignani E. Extracellular vesicles from equine mesenchymal stem cells decrease inflammation markers in chondrocytes in vitro. Equine Vet J 2022;54:1133-1143. [PMID: 34741769 PMCID: PMC9787580 DOI: 10.1111/evj.13537] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 10/29/2021] [Indexed: 12/30/2022]

Abstract

BACKGROUND

Mesenchymal stem cells (MSCs) have been used therapeutically in equine medicine. MSCs release extracellular vesicles (EVs), which affect cell processes by inhibiting cell apoptosis and regulating inflammation. To date, little is known about equine EVs and their regenerative properties.

OBJECTIVES

To characterise equine MSC-derived extracellular vesicles (EVs) and evaluate their effect on equine chondrocytes treated with pro-inflammatory cytokines in vitro.

STUDY DESIGN

In vitro experiments with randomised complete block design.

METHODS

Mesenchymal stem cells from bone marrow, adipose tissue, and synovial fluid were cultured in vitro. The MSC culture medium was centrifuged and filtered. Isolated particles were analysed for size and concentration (total number of particles per mL). Transmission electron microscopy analysis was performed to evaluate the morphology and CD9 expression of the particles. Chondrocytes from healthy equines were treated with the inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor-alpha. MSC-derived EVs from bone marrow and synovial fluid cells were added as co-treatments in vitro. Gene expression analysis by real-time PCR was performed to evaluate the effects of EVs.

RESULTS

The particles isolated from MSCs derived from different tissues did not differ significantly in size and concentration. The particles had a round-like shape and positively expressed CD9. EVs from bone marrow cells displayed reduced expression of metalloproteinase-13.

MAIN LIMITATIONS

Sample size and characterisation of the content of EVs.

CONCLUSIONS

EVs isolated from equine bone marrow MSCs reduced metalloproteinase 13 gene expression; this gene encodes an enzyme related to cartilage degradation in inflamed chondrocytes in vitro. EVs derived from MSCs can reduce inflammation and could potentially be used as an adjuvant treatment to improve tissue and cartilage repair in the articular pathologies.

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Tasma Z, Hou W, Damani T, Seddon K, Kang M, Ge Y, Hanlon D, Hollinshead F, Hisey CL, Chamley LW. Production of extracellular vesicles from equine embryo-derived mesenchymal stromal cells. Reproduction 2022;164:143-154. [PMID: 35938796 DOI: 10.1530/rep-22-0215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Accepted: 08/08/2022] [Indexed: 12/15/2022]

Zhou X, Cao H, Guo J, Yuan Y, Ni G. Effects of BMSC-Derived EVs on Bone Metabolism. Pharmaceutics 2022;14:1012. [PMID: 35631601 PMCID: PMC9146387 DOI: 10.3390/pharmaceutics14051012] [Citation(s) in RCA: 45] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2022] [Revised: 05/03/2022] [Accepted: 05/06/2022] [Indexed: 01/27/2023] Open

Lederer CW, Koniali L, Buerki-Thurnherr T, Papasavva PL, La Grutta S, Licari A, Staud F, Bonifazi D, Kleanthous M. Catching Them Early: Framework Parameters and Progress for Prenatal and Childhood Application of Advanced Therapies. Pharmaceutics 2022;14:pharmaceutics14040793. [PMID: 35456627 PMCID: PMC9031205 DOI: 10.3390/pharmaceutics14040793] [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: 02/28/2022] [Revised: 03/29/2022] [Accepted: 04/01/2022] [Indexed: 01/19/2023] Open

Brown SV, Dewitt S, Clayton A, Waddington RJ. Identifying the Efficacy of Extracellular Vesicles in Osteogenic Differentiation: An EV-Lution in Regenerative Medicine. FRONTIERS IN DENTAL MEDICINE 2022. [DOI: 10.3389/fdmed.2022.849724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open

Abstract Mesenchymal stromal cells (MSCs) have long been the focus for regenerative medicine and the restoration of damaged or aging cells throughout the body. However, the efficacy of MSCs in cell-based therapy still remains unpredictable and carries with it enumerable risks. It is estimated that only 3-10% of MSCs survive transplantation, and there remains undefined and highly variable heterogeneous biological potency within these administered cell populations. The mode of action points to secreted factors produced by MSCs rather than the reliance on engraftment. Hence harnessing such secreted elements as a replacement for live-cell therapies is attractive. Extracellular vesicles (EVs) are heterogenous lipid bounded structures, secreted by cells. They comprise a complex repertoire of molecules including RNA, proteins and other factors that facilitate cell-to-cell communication. Described as protected signaling centers, EVs can modify the cellular activity of recipient cells and are emerging as a credible alternative to cell-based therapies. EV therapeutics demonstrate beneficial roles for wound healing by preventing apoptosis, moderating immune responses, and stimulating angiogenesis, in addition to promoting cell proliferation and differentiation required for tissue matrix synthesis. Significantly, EVs maintain their signaling function following transplantation, circumventing the issues related to cell-based therapies. However, EV research is still in its infancy in terms of their utility as medicinal agents, with many questions still surrounding mechanistic understanding, optimal sourcing, and isolation of EVs for regenerative medicine. This review will consider the efficacy of using cell-derived EVs compared to traditional cell-based therapies for bone repair and regeneration. We discuss the factors to consider in developing productive lines of inquiry and establishment of standardized protocols so that EVs can be harnessed from optimal secretome production, to deliver reproducible and effective therapies. Collapse

Infante A, Cabodevilla L, Gener B, Rodríguez CI. Circulating TGF-β Pathway in Osteogenesis Imperfecta Pediatric Patients Subjected to MSCs-Based Cell Therapy. Front Cell Dev Biol 2022;10:830928. [PMID: 35223854 PMCID: PMC8865676 DOI: 10.3389/fcell.2022.830928] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2021] [Accepted: 01/24/2022] [Indexed: 11/13/2022] Open

Educating EVs to Improve Bone Regeneration: Getting Closer to the Clinic. Int J Mol Sci 2022;23:ijms23031865. [PMID: 35163787 PMCID: PMC8836395 DOI: 10.3390/ijms23031865] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 01/28/2022] [Accepted: 02/05/2022] [Indexed: 12/11/2022] Open

Vermeulen S, Birgani ZT, Habibovic P. Biomaterial-induced pathway modulation for bone regeneration. Biomaterials 2022;283:121431. [DOI: 10.1016/j.biomaterials.2022.121431] [Citation(s) in RCA: 56] [Impact Index Per Article: 18.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/28/2022] [Accepted: 02/17/2022] [Indexed: 12/18/2022]

Culture Condition of Bone Marrow Stromal Cells Affects Quantity and Quality of the Extracellular Vesicles. Int J Mol Sci 2022;23:ijms23031017. [PMID: 35162938 PMCID: PMC8834965 DOI: 10.3390/ijms23031017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 01/15/2022] [Accepted: 01/16/2022] [Indexed: 12/16/2022] Open

Mesenchymal Stem Cell-Based Therapy as a New Approach for the Treatment of Systemic Sclerosis. Clin Rev Allergy Immunol 2022;64:284-320. [PMID: 35031958 DOI: 10.1007/s12016-021-08892-z] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/24/2021] [Indexed: 12/13/2022]

Scheiber AL, Wilkinson KJ, Suzuki A, Enomoto-Iwamoto M, Kaito T, Cheah KS, Iwamoto M, Leikin S, Otsuru S. 4PBA reduces growth deficiency in osteogenesis imperfecta by enhancing transition of hypertrophic chondrocytes to osteoblasts. JCI Insight 2022;7:149636. [PMID: 34990412 PMCID: PMC8855815 DOI: 10.1172/jci.insight.149636] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 12/21/2021] [Indexed: 11/17/2022] Open

Bravo Vázquez LA, Moreno Becerril MY, Mora Hernández EO, de León Carmona GG, Aguirre Padilla ME, Chakraborty S, Bandyopadhyay A, Paul S. The Emerging Role of MicroRNAs in Bone Diseases and Their Therapeutic Potential. MOLECULES (BASEL, SWITZERLAND) 2021;27:molecules27010211. [PMID: 35011442 PMCID: PMC8746945 DOI: 10.3390/molecules27010211] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/16/2021] [Accepted: 12/24/2021] [Indexed: 01/24/2023]

Kang IH, Baliga UK, Wu Y, Mehrotra S, Yao H, LaRue AC, Mehrotra M. Hematopoietic stem cell-derived functional osteoblasts exhibit therapeutic efficacy in a murine model of osteogenesis imperfecta. Stem Cells 2021;39:1457-1477. [PMID: 34224636 DOI: 10.1002/stem.3432] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Revised: 05/03/2021] [Accepted: 06/08/2021] [Indexed: 11/08/2022]

Affiliation(s)

In-Hong Kang Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
Uday K Baliga Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
Yongren Wu Department of Orthopedics, Medical University of South Carolina, Charleston, South Carolina, USA Department of Bioengineering, Clemson University, Clemson, South Carolina, USA Clemson-MUSC Joint Bioengineering Program, Medical University of South Carolina, Charleston, South Carolina, USA
Shikhar Mehrotra Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA
Hai Yao Department of Orthopedics, Medical University of South Carolina, Charleston, South Carolina, USA Department of Bioengineering, Clemson University, Clemson, South Carolina, USA Clemson-MUSC Joint Bioengineering Program, Medical University of South Carolina, Charleston, South Carolina, USA Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA
Amanda C LaRue Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA Ralph H. Johnson VA Medical Center, Charleston, South Carolina, USA
Meenal Mehrotra Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, South Carolina, USA Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina, USA Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA Center for Oral Health Research, Medical University of South Carolina, Charleston, South Carolina, USA

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Infante A, Rodríguez CI. Cell and Cell-Free Therapies to Counteract Human Premature and Physiological Aging: MSCs Come to Light. J Pers Med 2021;11:1043. [PMID: 34683184 PMCID: PMC8541473 DOI: 10.3390/jpm11101043] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 10/13/2021] [Accepted: 10/14/2021] [Indexed: 12/13/2022] Open

Gorgun C, Palamà MEF, Reverberi D, Gagliani MC, Cortese K, Tasso R, Gentili C. Role of extracellular vesicles from adipose tissue- and bone marrow-mesenchymal stromal cells in endothelial proliferation and chondrogenesis. Stem Cells Transl Med 2021;10:1680-1695. [PMID: 34480533 PMCID: PMC8641083 DOI: 10.1002/sctm.21-0107] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 06/15/2021] [Accepted: 07/06/2021] [Indexed: 12/12/2022] Open

Chen H, Liu O, Chen S, Zhou Y. Aging and Mesenchymal Stem Cells: Therapeutic Opportunities and Challenges in the Older Group. Gerontology 2021;68:339-352. [PMID: 34161948 DOI: 10.1159/000516668] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2021] [Accepted: 04/07/2021] [Indexed: 11/19/2022] Open

Murali VP, Holmes CA. Mesenchymal stromal cell-derived extracellular vesicles for bone regeneration therapy. Bone Rep 2021;14:101093. [PMID: 34095360 PMCID: PMC8166743 DOI: 10.1016/j.bonr.2021.101093] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 05/10/2021] [Accepted: 05/12/2021] [Indexed: 12/24/2022] Open

Wang X, Thomsen P. Mesenchymal stem cell-derived small extracellular vesicles and bone regeneration. Basic Clin Pharmacol Toxicol 2021;128:18-36. [PMID: 32780530 PMCID: PMC7820981 DOI: 10.1111/bcpt.13478] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 08/03/2020] [Accepted: 08/06/2020] [Indexed: 12/20/2022]

Infante A, Gener B, Vázquez M, Olivares N, Arrieta A, Grau G, Llano I, Madero L, Bueno AM, Sagastizabal B, Gerovska D, Araúzo‐Bravo MJ, Astigarraga I, Rodríguez CI. Reiterative infusions of MSCs improve pediatric osteogenesis imperfecta eliciting a pro-osteogenic paracrine response: TERCELOI clinical trial. Clin Transl Med 2021;11:e265. [PMID: 33463067 PMCID: PMC7805402 DOI: 10.1002/ctm2.265] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Revised: 12/04/2020] [Accepted: 12/07/2020] [Indexed: 02/06/2023] Open

Arthur A, Gronthos S. Clinical Application of Bone Marrow Mesenchymal Stem/Stromal Cells to Repair Skeletal Tissue. Int J Mol Sci 2020;21:E9759. [PMID: 33371306 PMCID: PMC7767389 DOI: 10.3390/ijms21249759] [Citation(s) in RCA: 158] [Impact Index Per Article: 31.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 12/14/2020] [Accepted: 12/16/2020] [Indexed: 12/13/2022] Open

Zinger A, Brozovich A, Pasto A, Sushnitha M, Martinez JO, Evangelopoulos M, Boada C, Tasciotti E, Taraballi F. Bioinspired Extracellular Vesicles: Lessons Learned From Nature for Biomedicine and Bioengineering. NANOMATERIALS (BASEL, SWITZERLAND) 2020;10:E2172. [PMID: 33143238 PMCID: PMC7693812 DOI: 10.3390/nano10112172] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/02/2020] [Revised: 10/23/2020] [Accepted: 10/23/2020] [Indexed: 12/14/2022]

Affiliation(s)

Assaf Zinger Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX 77030, USA; (A.B.); (A.P.); (M.S.); (J.O.M.); (M.E.); (C.B.); (E.T.) Department of Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX 77030, USA
Ava Brozovich Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX 77030, USA; (A.B.); (A.P.); (M.S.); (J.O.M.); (M.E.); (C.B.); (E.T.) Department of Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX 77030, USA Texas A&M College of Medicine, Bryan, TX 77807, USA
Anna Pasto Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX 77030, USA; (A.B.); (A.P.); (M.S.); (J.O.M.); (M.E.); (C.B.); (E.T.) Department of Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX 77030, USA Department of Inflammation and Immunology, Humanitas Clinical and Research Center, 20089 Rozzano, Italy
Manuela Sushnitha Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX 77030, USA; (A.B.); (A.P.); (M.S.); (J.O.M.); (M.E.); (C.B.); (E.T.) Department of Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX 77030, USA Department of Bioengineering, Rice University, Houston, TX 77030, USA
Jonathan O. Martinez Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX 77030, USA; (A.B.); (A.P.); (M.S.); (J.O.M.); (M.E.); (C.B.); (E.T.) Department of Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX 77030, USA
Michael Evangelopoulos Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX 77030, USA; (A.B.); (A.P.); (M.S.); (J.O.M.); (M.E.); (C.B.); (E.T.) Department of Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX 77030, USA
Christian Boada Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX 77030, USA; (A.B.); (A.P.); (M.S.); (J.O.M.); (M.E.); (C.B.); (E.T.) Department of Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX 77030, USA
Ennio Tasciotti Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX 77030, USA; (A.B.); (A.P.); (M.S.); (J.O.M.); (M.E.); (C.B.); (E.T.) Department of Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX 77030, USA Biotechnology Program, San Raffaele University, Via di Val Cannuta, 247, 00166 Roma RM, Italy
Francesca Taraballi Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, TX 77030, USA; (A.B.); (A.P.); (M.S.); (J.O.M.); (M.E.); (C.B.); (E.T.) Department of Orthopedics and Sports Medicine, Houston Methodist Hospital, Houston, TX 77030, USA

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Marom R, Rabenhorst BM, Morello R. Osteogenesis imperfecta: an update on clinical features and therapies. Eur J Endocrinol 2020;183:R95-R106. [PMID: 32621590 PMCID: PMC7694877 DOI: 10.1530/eje-20-0299] [Citation(s) in RCA: 148] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Accepted: 07/02/2020] [Indexed: 12/12/2022]

Sonoda S, Murata S, Nishida K, Kato H, Uehara N, Kyumoto YN, Yamaza H, Takahashi I, Kukita T, Yamaza T. Extracellular vesicles from deciduous pulp stem cells recover bone loss by regulating telomerase activity in an osteoporosis mouse model. Stem Cell Res Ther 2020;11:296. [PMID: 32680564 PMCID: PMC7367365 DOI: 10.1186/s13287-020-01818-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 06/23/2020] [Accepted: 07/08/2020] [Indexed: 02/06/2023] Open

Abstract

BACKGROUND

Systemic transplantation of stem cells from human exfoliated deciduous teeth (SHED) recovers bone loss in animal models of osteoporosis; however, the mechanisms underlying this remain unclear. Here, we hypothesized that trophic factors within SHED-releasing extracellular vesicles (SHED-EVs) rescue osteoporotic phenotype.

METHODS

EVs were isolated from culture supernatant of SHED. SHED-EVs were treated with or without ribonuclease and systemically administrated into ovariectomized mice, followed by the function of recipient bone marrow mesenchymal stem cells (BMMSCs) including telomerase activity, osteoblast differentiation, and sepmaphorine-3A (SEMA3A) secretion. Subsequently, human BMMSCs were stimulated by SHED-EVs with or without ribonuclease treatment, and then human BMMSCs were examined regarding the function of telomerase activity, osteoblast differentiation, and SEMA3A secretion. Furthermore, SHED-EV-treated human BMMSCs were subcutaneously transplanted into the dorsal skin of immunocompromised mice with hydroxyapatite tricalcium phosphate (HA/TCP) careers and analyzed the de novo bone-forming ability.

RESULTS

We revealed that systemic SHED-EV-infusion recovered bone volume in ovariectomized mice and improved the function of recipient BMMSCs by rescuing the mRNA levels of Tert and telomerase activity, osteoblast differentiation, and SEMA3A secretion. Ribonuclease treatment depleted RNAs, including microRNAs, within SHED-EVs, and these RNA-depleted SHED-EVs attenuated SHED-EV-rescued function of recipient BMMSCs in the ovariectomized mice. These findings were supported by in vitro assays using human BMMSCs incubated with SHED-EVs.

CONCLUSION

Collectively, our findings suggest that SHED-secreted RNAs, such as microRNAs, play a crucial role in treating postmenopausal osteoporosis by targeting the telomerase activity of recipient BMMSCs.

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Affiliation(s)

Soichiro Sonoda Department of Molecular Cell Biology and Oral Anatomy, Division of Oral Biological Sciences, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
Sara Murata Department of Molecular Cell Biology and Oral Anatomy, Division of Oral Biological Sciences, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan Section of Orthodontics and Dentofacial Orthopedics, Division of Oral Health, Growth & Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
Kento Nishida Department of Molecular Cell Biology and Oral Anatomy, Division of Oral Biological Sciences, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
Hiroki Kato Department of Molecular Cell Biology and Oral Anatomy, Division of Oral Biological Sciences, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
Norihisa Uehara Department of Molecular Cell Biology and Oral Anatomy, Division of Oral Biological Sciences, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
Yukari N Kyumoto Department of Molecular Cell Biology and Oral Anatomy, Division of Oral Biological Sciences, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
Haruyoshi Yamaza Department of Pediatric Dentistry, Division of Oral Health, Growth & Development, Graduate School of Dental Science, Kyushu University, Fukuoka, Japan
Ichiro Takahashi Section of Orthodontics and Dentofacial Orthopedics, Division of Oral Health, Growth & Development, Faculty of Dental Science, Kyushu University, Fukuoka, Japan
Toshio Kukita Department of Molecular Cell Biology and Oral Anatomy, Division of Oral Biological Sciences, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan
Takayoshi Yamaza Department of Molecular Cell Biology and Oral Anatomy, Division of Oral Biological Sciences, Graduate School of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

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Iyer SR, Scheiber AL, Yarowsky P, Henn RF, Otsuru S, Lovering RM. Exosomes Isolated From Platelet-Rich Plasma and Mesenchymal Stem Cells Promote Recovery of Function After Muscle Injury. Am J Sports Med 2020;48:2277-2286. [PMID: 32543878 DOI: 10.1177/0363546520926462] [Citation(s) in RCA: 57] [Impact Index Per Article: 11.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]

Abstract

BACKGROUND

Clinical use of platelet-rich plasma (PRP) and mesenchymal stem cells (MSCs) has gained momentum as treatment for muscle injuries. Exosomes, or small cell-derived vesicles, could be helpful if they could deliver the same or better physiological effect without cell transplantation into the muscle.

HYPOTHESIS

Local delivery of exosomes derived from PRP (PRP-exos) or MSCs (MSC-exos) to injured muscles hastens recovery of contractile function.

STUDY DESIGN

Controlled laboratory study.

METHODS

In a rat model, platelets were isolated from blood, and MSCs were isolated from bone marrow and expanded in culture; exosomes from both were isolated through ultracentrifugation. The tibialis anterior muscles were injured in vivo using maximal lengthening contractions. Muscles were injected with PRP-exos or MSC-exos (immediately after injury and 5 and 10 days after injury); controls received an equal volume of saline. Histological and biochemical analysis was performed on tissues for all groups.

RESULTS

Injury resulted in a significant loss of maximal isometric torque (66% ± 3%) that gradually recovered over 2 weeks. Both PRP-exos and MSC-exos accelerated recovery, with similar faster recovery of contractile function over the saline-treated group at 5, 10, and 15 days after injury (P < .001). A significant increase in centrally nucleated fibers was seen with both types of exosome groups by day 15 (P < .01). Genes involved in skeletal muscle regeneration were modulated by different exosomes. Muscles treated with PRP-exos had increased expression of Myogenin gene (P < .05), whereas muscles treated with MSC-exos had reduced expression of TGF-β (P < .05) at 10 days after muscle injury.

CONCLUSION

Exosomes derived from PRP or MSCs can facilitate recovery after a muscle strain injury in a small-animal model likely because of factors that can modulate inflammation, fibrosis, and myogenesis.

CLINICAL RELEVANCE

Given their small size, low immunogenicity, and ease with which they can be obtained, exosomes could represent a novel therapy for many orthopaedic ailments.

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Benavides-Castellanos MP, Garzón-Orjuela N, Linero I. Effectiveness of mesenchymal stem cell-conditioned medium in bone regeneration in animal and human models: a systematic review and meta-analysis. CELL REGENERATION (LONDON, ENGLAND) 2020;9:5. [PMID: 32588230 PMCID: PMC7306835 DOI: 10.1186/s13619-020-00047-3] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Accepted: 11/18/2019] [Indexed: 12/13/2022]

Abstract

BACKGROUND

Given the limitations of current therapies for the reconstruction of bone defects, regenerative medicine has arisen as a new therapeutic strategy along with mesenchymal stem cells (MSCs), which, because of their osteogenic potential and immunomodulatory properties, have emerged as a promising alternative for the treatment of bone injuries. In vivo studies have demonstrated that MSCs have a positive effect on regeneration due to their secretion of cytokines and growth factors that, when collected in conditioned medium (MSC-CM) and applied to an injured tissue, can modulate and promote the formation of new tissue.

OBJECTIVE

To evaluate the effectiveness of application of conditioned medium derived from mesenchymal stem cells in bone regeneration in animal and human models.

METHODS

We conducted a systematic review with a comprehensive search through February of 2018 using several electronic databases (MEDLINE, EMBASE, SCOPUS, CENTRAL (Ovid), and LILACS), and we also used the "snowballing technique". Articles that met the inclusion criteria were selected through abstract review and subsequent assessment of the full text. We assessed the risk of bias with the SYRCLE and Cochrane tools, and three meta-analyses were performed.

RESULTS

We included 21 articles, 19 of which used animal models and 2 of which used human models. In animal models, the application of MSC-CM significantly increased the regeneration of bone defects in comparison with control groups. Human studies reported early mineralization in regenerated bones, and no bone resorption, inflammation, nor local or systemic alterations were observed in any case. The meta-analysis showed an overall favorable effect of the application of MSC-CM.

CONCLUSIONS

The application of MSC-CM to bone defects has a positive and favorable effect on the repair and regeneration of bone tissue, particularly in animal models. It is necessary to perform additional studies to support the application of MSC-CM in clinical practice.

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Varderidou-Minasian S, Lorenowicz MJ. Mesenchymal stromal/stem cell-derived extracellular vesicles in tissue repair: challenges and opportunities. Theranostics 2020;10:5979-5997. [PMID: 32483432 PMCID: PMC7254996 DOI: 10.7150/thno.40122] [Citation(s) in RCA: 181] [Impact Index Per Article: 36.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2019] [Accepted: 02/24/2020] [Indexed: 02/07/2023] Open

Therapeutic Advances of Stem Cell-Derived Extracellular Vesicles in Regenerative Medicine. Cells 2020;9:cells9030707. [PMID: 32183102 PMCID: PMC7140663 DOI: 10.3390/cells9030707] [Citation(s) in RCA: 54] [Impact Index Per Article: 10.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 03/07/2020] [Accepted: 03/10/2020] [Indexed: 12/14/2022] Open

Marzin P, Cormier-Daire V. New perspectives on the treatment of skeletal dysplasia. Ther Adv Endocrinol Metab 2020;11:2042018820904016. [PMID: 32166011 PMCID: PMC7054735 DOI: 10.1177/2042018820904016] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2019] [Accepted: 01/13/2020] [Indexed: 12/19/2022] Open

Zhou Y, Xiao Y. The Development of Extracellular Vesicle-Integrated Biomaterials for Bone Regeneration. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020;1250:97-108. [PMID: 32601940 DOI: 10.1007/978-981-15-3262-7_7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]

Use of Mesenchymal Stem/Stromal Cells for Pediatric Orthopedic Applications. Tech Orthop 2019. [DOI: 10.1097/bto.0000000000000351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]

Medhat D, Rodríguez CI, Infante A. Immunomodulatory Effects of MSCs in Bone Healing. Int J Mol Sci 2019;20:ijms20215467. [PMID: 31684035 PMCID: PMC6862454 DOI: 10.3390/ijms20215467] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2019] [Revised: 10/29/2019] [Accepted: 10/30/2019] [Indexed: 12/29/2022] Open

Mitxitorena I, Infante A, Gener B, Rodríguez CI. Suitability and limitations of mesenchymal stem cells to elucidate human bone illness. World J Stem Cells 2019;11:578-593. [PMID: 31616536 PMCID: PMC6789184 DOI: 10.4252/wjsc.v11.i9.578] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Revised: 07/31/2019] [Accepted: 08/27/2019] [Indexed: 02/06/2023] Open

Yao X, Wei W, Wang X, Chenglin L, Björklund M, Ouyang H. Stem cell derived exosomes: microRNA therapy for age-related musculoskeletal disorders. Biomaterials 2019;224:119492. [PMID: 31557588 DOI: 10.1016/j.biomaterials.2019.119492] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2019] [Revised: 09/09/2019] [Accepted: 09/11/2019] [Indexed: 12/12/2022]