Therapeutic potential of miR-10a overexpressing mesenchymal stem cell-derived extracellular vesicles in modulating inflammation in collagen-induced arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune condition that leads to joint damage. Mesenchymal stem cells (MSCs) are being recognized as a promising treatment option because of their capacity to modulate immune responses. Their therapeutic effects are mediated by released extracellular vesicles (EVs) which contain microRNAs known to influence inflammatory processes. This research focused on the impact of bone marrow MSC (BM-MSC)-derived EVs overexpressing miR-10a on cytokine production in a mouse model of collagen-induced arthritis (CIA). miR-10a was overexpressed in MSCs derived from bone marrow using Transfectamin. EVs were then isolated from the culture media of both miR-control and miR-10a-modified MSCs. Immunizing mice established the CIA model with type II collagen, after which they received either miR-control or miR-10a-enriched MSC-EVs. The severity of arthritis was evaluated through joint swelling measurements, and the concentrations of pro-inflammatory cytokines (such as interleukin (IL)-17a, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α) alongside anti-inflammatory cytokines (including transforming growth factor (TGF)-β, IL-10, and IL-4) in the joints and serum were assessed using real-time PCR and enzyme-linked immunosorbent assay (ELISA), respectively. Our results indicated that treatment with miR-10a MSC-EVs led to a notable decrease in arthritis severity and joint damage in CIA mice. Furthermore, these EVs were found to lower levels of pro-inflammatory cytokines while enhancing anti-inflammatory cytokines compared to those treated with miR-control MSC-EVs. This study highlights how enhancing miR-10a expression can improve the therapeutic efficacy of MSC-EVs by altering the cytokine environment in CIA models.