T-Regulatory Cells Confer Increased Myelination And Stem Cell Activity After Stroke-Induced White Matter Injury
JOURNAL OF CLINICAL MEDICINE(2019)
Abstract
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-regs) 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-reg 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-regs. OPCs were cultured and then exposed to OGD/R. BMSCs with or without T-regs were added to the co-culture immediately after ischemia. The T-regs were depleted by running the BMSCs through a column containing a magnetic substrate. Fibroblast growth factor beta (FGF-) and interleukin 6 (IL-6) ELISAs determined BMSC activity levels. Immunohistochemistry assessed OPC differentiation. OPCs cultured with BMSCs containing their endogenous T-regs showed increased myelin production compared to the BMSCs with depleted T-regs. IL-6 and FGF- were increased in the group cultured with T-regs. Collectively, these results suggest that BMSCs containing T-regs are more therapeutically active, and that T-regs have beneficial effects on OPCs subjected to ischemia. T-regs play an important role in stem cell therapy and can potentially treat white matter injury post-stroke.
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Key words
bone marrow-derived stem cells,mesenchymal stem cells,T-regulatory cells,white matter injury,stroke,oligodendrocytes,oligodendrocyte precursor cells,oxygen-glucose deprivation,reoxygenation
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