Archives of Biological Sciences 2024 Volume 76, Issue 4, Pages: 399-407
https://doi.org/10.2298/ABS240630030G
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Mesenchymal stem cell-derived extracellular vesicles enriched with miR-124 exhibit anti-inflammatory effects in collagen-induced arthritis
Guo Zhonghua 
(Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, China)
He Mengyuan (Henan University of Traditional Chinese Medicine, Zhengzhou City, Henan Province, China, Graduate student)
Shi Dongliang (Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, China)
Zhang Zhongbo (Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, China)
Wang Lisha (Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, China)
Ren Bowen (Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, China)
Wang Yunfei (Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, China)
Wang Junjie (Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, China)
Yang Shaoxiang (Department of Orthopedics, Henan Provincial Hospital of Traditional Chinese Medicine, Zhengzhou City, Henan Province, China)
Yu Hongchao (Department of Orthopedics, Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang City, Shaanxi Province, China), Hy13468505752@outlook.com
Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by joint inflammation, leading to pain, swelling, stiffness, and joint damage. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) hold significant promise as therapeutic agents owing to their potent paracrine activities. This study investigated the anti-inflammatory effects of human umbilical cord-derived MSC (hUCSC)-EVs overexpressing miR-124 in collagen-induced arthritis (CIA). hUCSCs were transfected with miR-124, and hUCSC-EVs were isolated and characterized. Arthritis was induced in mice by collagen injection, followed by intravenous administration of miR-124 EVs, miR-control, or vehicle. Cytokine levels, including interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, IL-10, and transforming growth factor (TGF)-β, were measured in the joints using real-time PCR by enzyme-linked immunosorbent assay (ELISA). miR-124-hUCSC-EVs showed enrichment of miR-124. In arthritic mice, intravenous treatment with miR-124 EVs significantly reduced the clinical score, increased anti-inflammatory cytokines IL-10 and TGF-β, and lowered inflammatory cytokines IL-6, TNF-α, and IL-1β in the joints. This study shows that miR-124 EVs have anti-inflammatory activity in arthritis by suppressing pro-inflammatory cytokines through miR-124 overexpression. MSC-EVs overexpressed with inflammation-modulating miRNAs offer a promising cell-free approach for treating inflammatory arthritis.
Keywords: mesenchymal stem cells, extracellular vesicles, exosome, arthritis, cytokine
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