T-Regulatory Cells Confer Increased Myelination and Stem Cell Activity after Stroke-Induced White Matter Injury.

Stroke-induced hypoxia causes oligodendrocyte death due to inflammation, lack of oxygen and exacerbation of cell death. Bone marrow-derived stem cells (BMSCs) possess an endogenous population of T-regulatory cells (T) which reduce secretion of pro-inflammatory cytokines that lead to secondary cell death. Here, we hypothesize that oligodendrocyte progenitor cells (OPCs) cultured with BMSCs containing their native T population show greater cell viability, less pro-inflammatory cytokine secretion and greater myelin production after exposure to oxygen-glucose deprivation and reoxygenation (OGD/R) than OPCs cultured without T. OPCs were cultured and then exposed to OGD/R. BMSCs with or without T were added to the co-culture immediately after ischemia. The T were depleted by running the BMSCs through a column containing a magnetic substrate. Fibroblast growth factor beta (FGF-β) and interleukin 6 (IL-6) ELISAs determined BMSC activity levels. Immunohistochemistry assessed OPC differentiation. OPCs cultured with BMSCs containing their endogenous T showed increased myelin production compared to the BMSCs with depleted T. IL-6 and FGF-β were increased in the group cultured with T. Collectively, these results suggest that BMSCs containing T are more therapeutically active, and that T have beneficial effects on OPCs subjected to ischemia. T play an important role in stem cell therapy and can potentially treat white matter injury post-stroke.