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Published on: October 4, 2021
Cellular and Molecular Targets of Extracellular Vesicles from Mesenchymal Stem/Stromal Cells in Rheumatoid Arthritis
María José Alcaraz1, María Isabel Guillén1,2
1Interuniversity Research Institute for Molecular Recognition and Technological Development (IDM), University of Valencia, Polytechnic University of Valencia, Av. Vicent A. Estellés s/n, Burjassot, Valencia, Spain.
Abstract:
Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes progressive joint destruction. Despite the advances in the treatment of this condition there remains a clinical need for safe therapies leading to clinical remission. Mesenchymal stem/stromal cells (MSCs) play immunomodulatory and regenerative roles which can be partly mediated by their secretome. In recent years, the important contribution of extracellular vesicles (EVs) to MSC actions has received an increasing interest as a new therapeutic approach. We provide an extensive overview of the immunomodulatory properties of MSC EVs and their effects on articular cells such as fibroblast-like synoviocytes that play a central role in joint destruction. This review discusses the anti-arthritic effects of MSC EVs in vitro and in animal models of RA as well as their potential mechanisms. Recent preclinical data suggest that transfer of non-coding RNAs by MSC EVs regulates key signaling pathways involved in the pathogenesis of RA. We also examine a number of EV modifications for improving their anti-arthritic efficacy and carrier ability for drug delivery.
Insights
Mesenchymal stem/stromal cell (MSC) extracellular vesicles (EVs) show promise for treating rheumatoid arthritis (RA) by modulating immune responses and protecting joints. Further research into MSC EV modifications could enhance their therapeutic potential for RA.
Area of Science:
- Immunology
- Cell Biology
- Regenerative Medicine
Background:
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by progressive joint destruction.
- Current RA treatments still have unmet needs for safe and effective therapies achieving clinical remission.
- Mesenchymal stem/stromal cells (MSCs) possess immunomodulatory and regenerative capabilities, partly mediated by their secretome.
Approach:
- This review provides a comprehensive overview of the immunomodulatory properties of MSC-derived extracellular vesicles (EVs).
- It examines the effects of MSC EVs on articular cells, particularly fibroblast-like synoviocytes, crucial in RA pathogenesis.
- The review synthesizes in vitro and in vivo data on the anti-arthritic effects and potential mechanisms of MSC EVs.
Key Points:
- MSC EVs exhibit significant immunomodulatory functions relevant to treating RA.
- The transfer of non-coding RNAs by MSC EVs has been identified as a key mechanism regulating RA pathogenesis.
- MSC EVs demonstrate therapeutic potential in preclinical models of RA, reducing joint inflammation and destruction.
Conclusions:
- MSC EVs represent a promising cell-free therapeutic strategy for rheumatoid arthritis.
- Modifications to MSC EVs are being explored to enhance their anti-arthritic efficacy and drug delivery capabilities.
- Further investigation into MSC EV-based therapies could lead to novel treatments for RA patients.
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