Benefits of bone marrow-derived mesenchymal stem cells primed with estradiol in alleviating collagen-induced arthritis.

Objectives: To investigate the effects of the oestradiol (ES) pulsed bone marrow-derived mesenchymal stem cells (BM-MSC) to treat adjuvant-induced arthritis in Wistar rats. Materials and Methods: BM-MSCs were pulsed with ES (0, 10,100, and 1000 nM) for 24 hr. RA was induced by collagen and Freund's Complete Adjuvant into the base of the tail of Wistar rats. Results: The least effective concentration of ES that can promote potent anti-inflammatory properties in the MSC population is 100 nM. At this concentration, ES increases the inhibition of the polyclonal T lymphocyte proliferation, production of IDO, IL-10, Nitric oxide, and TGF-β, and expression of CXCR4 and CCR2 mRNA in the MSC population. Accordingly, the RA rats were treated with 2×106 MSCs or ES-pulsed MSCs (100 nM) on day 10 when all animals had developed signs of RA. ES-pulsed BM-MSCs reduced the severity of RA more profoundly than treatment with BM-MScs alone. The ability of ES-pulsed BM-MSCs to reduce symptoms and RA markers like CRP, RF, and nitric oxide was comparable to that of prednisolone. Prednisolone was more successful in reducing inflammatory cytokines than treatment with ES-pulsed BM-MSCs. ES-pulsed BM-MSCs were more successful in increasing anti-inflammatory cytokines than treatment with Prednisolone. The ability of ES-pulsed BM-MSCs to decrease the level of nitric oxide was comparable to that of prednisolone. Conclusion: ES-pulsed BM-MSCs may be a helpful strategy in RA control.