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Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?

ABSTRACT: Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since MSC-derived EVs retain the function of protocells and have lower immunogenicity, they have a wide range of prospective therapeutic applications with advantages over cell therapy. We describe some characteristics of MSC-EVs, and discuss their role in immune regulation and regeneration, with emphasis on the molecular mechanism and application of MSC-EVs in the treatment of fibrosis and support tissue repair. We also highlight current challenges in the clinical application of MSC-EVs and potential ways to overcome the problem of quality heterogeneity.

SUBMITTER: Kou M

PROVIDER: S-EPMC9252569 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?

Kou Meng M Huang Li L Yang Jinjuan J Chiang Zhixin Z Chen Shaoxiang S Liu Jie J Guo Liyan L Zhang Xiaoxian X Zhou Xiaoya X Xu Xiang X Yan Xiaomei X Wang Yan Y Zhang Jinqiu J Xu Aimin A Tse Hung-Fat HF Lian Qizhou Q

Cell death & disease 20220704 7

Mesenchymal stem cells (MSCs) can be widely isolated from various tissues including bone marrow, umbilical cord, and adipose tissue, with the potential for self-renewal and multipotent differentiation. There is compelling evidence that the therapeutic effect of MSCs mainly depends on their paracrine action. Extracellular vesicles (EVs) are fundamental paracrine effectors of MSCs and play a crucial role in intercellular communication, existing in various body fluids and cell supernatants. Since M ...[more]

PMID: 35787632

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Project description:BackgroundArticular cartilage injuries can lead to pain, stiffness, and reduced mobility, and may eventually progress to osteoarthritis (OA). Despite substantial research efforts, effective therapies capable of regenerating cartilage are still lacking. Mesenchymal stromal cells (MSCs) are known for their differentiation and immunomodulatory capabilities, yet challenges such as limited survival post-injection and inconsistent therapeutic outcomes hinder their clinical application. Recent evidence suggests that the beneficial effects of MSCs are largely mediated by their secreted small extracellular vesicles (sEVs), which have been shown to promote tissue repair and reduce inflammation. MSC-derived sEVs have shown promise in mitigating cartilage degradation and chondrocyte apoptosis, positioning them as a promising alternative to MSC-based therapies for OA treatment. This review explores the potential and limitations of MSC-derived sEVs in cartilage regeneration.Main textThis systematic review was conducted following PRISMA guidelines, with a comprehensive search of the Web of Science and Scopus databases for studies published between 2019 and 2024. A total of 223 records were identified, of which 132 articles were assessed for eligibility based on general selection criteria. After full-text screening, 60 articles were initially selected, comprising 58 in vitro studies and 40 in vivo studies. Following further exclusion based on specific criteria, 33 in vitro and 28 in vivo studies from a total of 47 scientific papers were included in the final qualitative synthesis. Most studies indicate that MSC-derived sEVs enhance chondrocyte proliferation, improve cartilage extracellular matrix composition, and reduce matrix-degrading enzymes and inflammation, thereby delaying OA progression.ConclusionA growing body of evidence supports the use of MSC-derived sEVs as a therapeutic tool for preventing OA progression, with most studies reporting beneficial effects on cartilage structure and function. However, challenges remain in optimizing and standardizing sEVs isolation, dosage, and delivery methods for clinical application. Further research is necessary to elucidate the mechanisms underlying sEVs-mediated cartilage regeneration and to facilitate their translation into effective OA therapies.

Dataset Information

Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?

Publications

Mesenchymal stem cell-derived extracellular vesicles for immunomodulation and regeneration: a next generation therapeutic tool?

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