Regulatory T-cells within bone marrow-derived stem cells actively confer immunomodulatory and neuroprotective effects against stroke

Regulatory T-cells (T-regs) may exert a neuroprotective effect on ischemic stroke by inhibiting both inflammation and effector T-cell activation. Transplantation of human bone marrow-derived stem cells (BMSCs) in ischemic stroke affords neuroprotection that results in part from the cells' anti-inflammatory property. However, the relationship between T-regs and BMSCs in treatment of ischemic stroke has not been fully elucidated. Here, we tested the hypothesis that T-regs within the BMSCs represent active mediators of immunomodulation and neuroprotection in experimental stroke. Primary rat neuronal cells were subjected to an oxygen-glucose deprivation and reperfusion (OGD/R) condition. The cells were re-perfused and co-cultured with T-regs and/or BMSCs. We detected a minority population of T-regs within BMSCs with both immunocytochemistry (ICC) and flow cytometry identifying cells expressing phenotypic markers of CD4, CD25, and FoxP3 protein. BMSCs with the native population of T-regs conferred maximal neuroprotection compared to the treatment conditions containing 0%, 10%, and 100% relative ratio T-regs. Increasing the T-reg population resulted in increased IL6 secretion and decreased FGF-beta secretion by BMSCs. This study shows that a minority population of T-regs exists within the therapeutic BMSC population, which serves as robust mediators of the immunomodulatory and neuroprotective effect provided by BMSC transplantation.