Placenta-derived mesenchymal stem cells improve airway hyperresponsiveness and inflammation in asthmatic rats by modulating the Th17/Treg balance

摘要

Mesenchymal stem cells (MSCs) possess reparative and immunoregulatory properties, representing a hope for stem cell-based treatments. However, the mechanisms by which transplanted MSCs affect T helper (Th)17/regulatory T cell (Treg) balance in asthma patients remain unclear. The aim of the present study was to assess the therapeutic effects of human placenta MSCs (hPMSCs) in asthma, and explore the underlying mechanisms; in addition, the impact of hPMSCs transplantation on Th17/Treg balance in lymph and serum samples from asthmatic animals was evaluated. Sprague-Dawley rats were sensitized and challenged with ovalbumin (OVA). Administration of hPMSCs from human placenta resulted in increased Th17 and Treg in lymph samples compared with peripheral blood specimens. Enhanced pause values in OVA-treated animals were significantly higher than those in the control and hPMSCs treatment groups. The numbers of total cells, macrophages, neutrophils, and eosinophils were markedly increased in the OVA group compared with those of control + hPMSCs and control groups. In addition, interleukin 10, forkhead box P3 (Foxp3) and Treg levels in lymph, peripheral blood and lung tissue samples from asthma rats were increased significantly following hPMSC transplantation. Furthermore, Foxp3 protein levels increased, while those of RAR-related orphan receptor gamma (ROR gamma t) decreased after hPMSCs transplantation compared with the asthma group. Reduced IL-17, ROR gamma t and Th17 levels were accompanied by reduced inflammatory cell infiltration, sub-epithelial smooth layer attenuation and mucus production in lung tissues. These results suggest that hPMSCs may improve airway hyperresponsiveness and inflammation by regulating the Th17/Treg balance in rats with asthma.