Human embryonic stem cell–derived mesenchymal stromal cells suppress inflammation in mouse models of rheumatoid arthritis and lung fibrosis by regulating T-cell function

Objectives Rheumatoid arthritis (RA) is characterized by an overactive immune system, with limited treatment options beyond immunosuppressive drugs or biological response modifiers. Human embryonic stem cells-derived mesenchymal stromal cells (hESC-MSCs) represent a novel alternative, possessing diverse immunomodulatory effects. In this study, we aimed to elucidate the therapeutic effects and underlying mechanisms of hESC-MSCs in treating RA. Methods MSC like cells were differentiated from hESC (hESC-MSCs) and cultured in vitro. Cell proliferation was assessed using CCK-8 assay and Ki-67 staining. Flow cytometry was utilized to analyze cell surface markers, T cell proliferation and immune cell infiltration. The collagen-induced arthritis (CIA) mouse model and bleomycin-induced model of lung fibrosis (BLE) were established and treated with hESC-MSCs intravenously for in vivo assessment. Pathological analyses, RT-qPCR and Western blotting were conducted to evaluate the efficacy of hESC-MSCs treatment. Results Intravenous transplantation of hESC-MSCs effectively reduced inflammation in CIA mice in this study. Furthermore, hESC-MSCs administration enhanced regulatory T (Treg) cell infiltration and activation. Additional findings suggest that hESC-MSCs may reduce lung fibrosis in BLE mouse models, indicating their potential to mitigate complications associated with RA progression. In vitro experiments revealed a significant inhibition of T cell activation and proliferation during co-culture with hESC-MSCs. Additionally, hESC-MSCs demonstrated enhanced proliferative capacity compared to traditional primary MSCs. Conclusion Transplantation of hESC-MSCs represents a promising therapeutic strategy for RA, potentially regulating T cell proliferation and differentiation.