Idiopathic pneumonia syndrome (IPS) is a serious and life-threatening lung complication following allogeneic hematopoietic stem cell transplantation (allo- HSCT) and currently no effective therapies exist. The present study was designed to determine whether transplantation of allogeneic murine compact bone derived- mesenchymal stem cells (CB-MSCs) could prevent the development of IPS.
We tested the effects of allogeneic CB-MSCs transplantation on IPS using an established murine model of IPS, wherein lethally irradiated male BALB/c (H-2d) recipient mice received bone marrow and spleen cells from female C57BL/6(H-2b) donors. Survival rates, body weight change, clinical GVHD scores, lung histological changes and wet-dry lung ratios were assessed after IPS induction. Mechanistically, concentrations of cytokines (TNF-alpha, IFN-gamma and IL-4) and chemokines (CCL5, CXCL9 and CXCL10) in bronchoalveolar lavage fluid (BALF) from the recipient mice were measured at different time point post-transplantation. CD4+CD25+Foxp3+ regulatory T cell (Treg) percentage, CCR5, CXCR3 and CCR7 expression on CD3+ T cells, and lung CXCR3, CCR5, CCR7, T-bet and GATA-3 mRNA levels were also evaluated at different time point post-transplantation.
In the IPS model, co-transplantation of CB-MSCs significantly attenuated the severity of lung injuries and increased the survival rate of mice compared to non-cotransplanted mice. Furthermore, a higher Treg percentages, reduced TNF-alpha, IFN-gamma, CCL5, CXCL9 and CXCL10 levels, CXCR3 and CCR5 down-regulation, as well as CCR7 up-regulation, were observed in MSCs co-transplantation mice. Additionally, the prophylactic effect of CB-MSCs was also associated with a shift of Th1/Th2 balance toward anti-inflammatory Th2 polarization.
Our present data suggested that allogeneic CB-MSCs attenuated the severity of IPS due to its profound immunomodulatory capacity in our murine model. This may offer a novel prophylactic approach for IPS patients after allo-HSCT.
No relevant conflicts of interest to declare.
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