Zarriello Sydney, Neal Elliot G, Kaneko Yuji, Borlongan Cesario V
Center of Excellence for Aging and Brain Repair, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.
Biomedical Research Concentration, Scholarly Concentrations Program, University of South Florida Morsani College of Medicine, Tampa, FL 33612, USA.
J Clin Med. 2019 Apr 19;8(4):537. doi: 10.3390/jcm8040537.
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.
中风诱导的缺氧会因炎症、缺氧和细胞死亡加剧而导致少突胶质细胞死亡。骨髓源性干细胞（BMSCs）含有内源性调节性T细胞（T细胞）群体，这些细胞可减少导致继发性细胞死亡的促炎细胞因子的分泌。在此，我们假设，与不含T细胞的骨髓间充质干细胞共培养的少突胶质前体细胞（OPCs）相比，与含有天然T细胞群体的骨髓间充质干细胞共培养的少突胶质前体细胞在暴露于氧糖剥夺和复氧（OGD/R）后表现出更高的细胞活力、更少的促炎细胞因子分泌和更多的髓磷脂生成。培养少突胶质前体细胞，然后使其暴露于氧糖剥夺和复氧环境。缺血后立即将含或不含T细胞的骨髓间充质干细胞添加到共培养体系中。通过含有磁性基质的柱子处理骨髓间充质干细胞以去除T细胞。用成纤维细胞生长因子β（FGF-β）和白细胞介素6（IL-6）酶联免疫吸附测定法测定骨髓间充质干细胞的活性水平。免疫组织化学评估少突胶质前体细胞的分化。与去除T细胞的骨髓间充质干细胞相比，与含有内源性T细胞的骨髓间充质干细胞共培养的少突胶质前体细胞髓磷脂生成增加。在含有T细胞的培养组中，IL-6和FGF-β增加。总体而言，这些结果表明含有T细胞的骨髓间充质干细胞具有更强的治疗活性，并且T细胞对遭受缺血的少突胶质前体细胞具有有益作用。T细胞在干细胞治疗中起重要作用，并且可能治疗中风后的白质损伤。
