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Mesenchymal Stromal Cells-Derived Extracellular Vesicles as Potential Treatments for Osteoarthritis.

ABSTRACT: Osteoarthritis (OA) is a degenerative disease of the joints characterized by cartilage damage and severe pain. Despite various pharmacological and surgical interventions, current therapies fail to halt OA progression, leading to high morbidity and an economic burden. Thus, there is an urgent need for alternative therapeutic approaches that can effectively address the underlying pathophysiology of OA. Extracellular Vesicles (EVs) derived from mesenchymal stromal cells (MSCs) represent a new paradigm in OA treatment. MSC-EVs are small membranous particles released by MSCs during culture, both in vitro and in vivo. They possess regenerative properties and can attenuate inflammation, thereby promoting cartilage healing. Importantly, MSC-EVs have several advantages over MSCs as cell-based therapies, including lower risks of immune reactions and ethical issues. Researchers have recently explored different strategies, such as modifying EVs to enhance their delivery, targeting efficiency, and security, with promising results. This article reviews how MSC-EVs can help treat OA and how they might work. It also briefly discusses the benefits and challenges of using MSC-EVs and talks about the possibility of allogeneic and autologous MSC-EVs for medical use.

SUBMITTER: Yuan S

PROVIDER: S-EPMC10385170 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Mesenchymal Stromal Cells-Derived Extracellular Vesicles as Potential Treatments for Osteoarthritis.

Yuan Shunling S Li Guangfeng G Zhang Jinbo J Chen Xiao X Su Jiacan J Zhou Fengjin F

Pharmaceutics 20230625 7

Osteoarthritis (OA) is a degenerative disease of the joints characterized by cartilage damage and severe pain. Despite various pharmacological and surgical interventions, current therapies fail to halt OA progression, leading to high morbidity and an economic burden. Thus, there is an urgent need for alternative therapeutic approaches that can effectively address the underlying pathophysiology of OA. Extracellular Vesicles (EVs) derived from mesenchymal stromal cells (MSCs) represent a new parad ...[more]

PMID: 37514001

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Project description:BackgroundMesenchymal 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.MethodsWe 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.ResultsFetal 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.ConclusionsThis 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.

Dataset Information

Mesenchymal Stromal Cells-Derived Extracellular Vesicles as Potential Treatments for Osteoarthritis.

Publications

Mesenchymal Stromal Cells-Derived Extracellular Vesicles as Potential Treatments for Osteoarthritis.

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