Preconditioning of bone marrow mesenchymal stem cells with sodium hydrosulfide enhances their therapeutic potential in type II collagen–induced arthritis rat model

Abstract

This study was conducted to evaluate the impact of sodium hydrogen sulfide (NaHS) on the therapeutic efficacy of bone marrow mesenchymal stem cells (BM-MSCs) in the treatment of collagen-induced arthritis (CIA) rats. MSCs were isolated and cultured from rat bone marrow, and their characteristics were determined. The CIA model was induced in rats by intradermal injections of type II collagen on days 0 and 21. A variety of treatments were administered, including naproxen, BM-MSCs, BM-MSC-conditioned media, NaHS, BM-MSCs preconditioned with NaHS, and BM-MSCs preconditioned with NaHS-conditioned media. The infused BM-MSCs homed to the bone trabeculae and cartilage of the knee joint, leading to significant improvements in gait scores and a reduction in paw withdrawal frequency (PWF). Treatment with BM-MSCs and NaHS also significantly suppressed serum levels of CRP, RF, and 14-3-3η, while downregulating TNF-α gene expression and MMP-1 protein levels in the synovial membrane. Histopathological analysis confirmed these biochemical and molecular genetic findings. Notably, CIA rats treated with BM-MSCs preconditioned with NaHS showed the most significant improvements, with outcomes closely resembling those of healthy controls. This study concludes that NaHS enhances the therapeutic efficacy of BM-MSC therapy for rheumatoid arthritis (RA) by augmenting their anti-inflammatory, immunomodulatory, and regenerative properties.

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