Jessie Jiang

Introduction. Osteoarthritis (OA) is a chronic painful disease characterized by cartilage damage and synovial inflammation. Approximately 15% of the global population has OA and it’s a leading cause of disability.¹ In OA a large number of inflammatory cells including synovial macrophages enter the synovial tissue of OA patients.¹ There are two types of macrophages: M1 which are pro-inflammatory and M2 which are anti-inflammatory. M1 macrophages accumulate in the synovial tissues of OA patients, and facilitate development of OA. ¹ Current treatment for OA focuses mostly on symptom alleviation and pain management. There’s a lack of effective treatments focused on repairing damaged cartilage, and reversing the pathogenesis of OA. ¹ A promising new avenue of treatment centers around macrophage polarization from M1 to M2 by stem cell exosomes. ¹ Methods. Exosomes isolated from murine BM-MSCs were incubated with macrophages from spleens of OA rats. The spleen macrophages were activated by LPS and ELISA was used to investigate the expression of activation markers.² OA rat models were used and divided into six groups differing in TGF-β1 or PBS simulation and if inhibitor negative control or miR-135b inhibitor was added.¹ BM-MSC exosomes from rat cartilages were incubated with macrophage RAW264.7 cell line and injected into the knee joint cavity of OA model rats. ⁴ Exosomes isolated from adipose derived stem cells (ADSCs) collected from adipose tissue from liposuction surgery of a healthy patient were incubated with activated synovial fibroblasts (SF) from an obese patient with OA.⁵ Results. BM-MSC exosomes in-vitro inhibit macrophage activation.² They reduce cartilage damage though inflammatory marker regulation by inducing expression of anti-inflammatory cytokines IL-10 and TGF-β1 and reducing expression of pro-inflammatory cytokines like IL-1β and TNF-α. ³ By treating OA rat models with TGF-β1 stimulated BM-MSC, the exosomes have increased levels of miR-135b which promote M2 macrophage polarization through repressing MAPK6 expression. ¹ Intra-articular injection of BM-MSC exosomes decreased pro-inflammatory cytokine levels and increased anti-inflammatory cytokines indicating M1 to M2 macrophage polarization occurred.⁴ Human-ADSC exosomes are effective at alleviating cartilage damage in OA human cells.⁵ Conclusion. Overall, exosomes are a promising avenue for future treatment of osteoarthritis especially because it’s been proven that human derived stem cell exosomes were effective at treating human cells with OA.⁵ Future research should be conducted in exploring the mechanism behind how exosomes induce macrophage polarization, increased use of human OA models, and the clinical efficacy of intra-articular injection of exosomes.^{1 4}

1.  Wang R, Xu B. TGF-β1-modified MSC-derived exosomal miR-135b attenuates cartilage injury via promoting M2 synovial macrophage polarization by targeting MAPK6. Cell Tissue Res. 2021;384(1):113-127. doi:10.1007/s00441-020-03319-1
2. Cosenza S, Ruiz M, Toupet K, Jorgensen C, Noël D. Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis. Sci Rep. 2017;7(1):16214. Published 2017 Nov 24. doi:10.1038/s41598-017-15376-8
3. Zhang S, Chuah SJ, Lai RC, Hui JHP, Lim SK, Toh WS. MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity. Biomaterials. 2018;156:16-27. doi:10.1016/j.biomaterials.2017.11.028
4. Zhang J, Rong Y, Luo C, Cui W. Bone marrow mesenchymal stem cell-derived exosomes prevent osteoarthritis by regulating synovial macrophage polarization. Aging (Albany NY). 2020;12(24):25138-25152. doi:10.18632/aging.104110
5. Zhao C, Chen JY, Peng WM, Yuan B, Bi Q, Xu YJ. Exosomes from adipose‑derived stem cells promote chondrogenesis and suppress inflammation by upregulating miR‑145 and miR‑221. Mol Med Rep. 2020;21(4):1881-1889. doi:10.3892/mmr.2020.10982