Department of Neurology, Brain Research Institute, Niigata University, 1-757 Asahimachi-dori, Chuoku, Niigata, 951-8585, Japan.
Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe, 2-2 Minatojima-Minamimachi, Kobe, 650-0047, Japan.
Sci Rep. 2019 Nov 14;9(1):16819. doi: 10.1038/s41598-019-53418-5.
Cell therapies that invoke pleiotropic mechanisms may facilitate functional recovery in patients with stroke. Based on previous experiments using microglia preconditioned by oxygen-glucose deprivation, we hypothesized that the administration of peripheral blood mononuclear cells (PBMCs) preconditioned by oxygen-glucose deprivation (OGD-PBMCs) to be a therapeutic strategy for ischemic stroke. Here, OGD-PBMCs were identified to secrete remodelling factors, including the vascular endothelial growth factor and transforming growth factor-β in vitro, while intra-arterial administration of OGD-PBMCs at 7 days after focal cerebral ischemia prompted expression of such factors in the brain parenchyma at 28 days following focal cerebral ischemia in vivo. Furthermore, administration of OGD-PBMCs induced an increasing number of stage-specific embryonic antigen-3-positive cells both in vitro and in vivo. Finally, it was found to prompt angiogenesis and axonal outgrowth, and functional recovery after cerebral ischemia. In conclusion, the administration of OGD-PBMCs might be a novel therapeutic strategy against ischemic stroke.
细胞疗法通过诱导多效性机制可能有助于中风患者的功能恢复。基于先前使用氧葡萄糖剥夺预处理的小胶质细胞的实验,我们假设给予氧葡萄糖剥夺预处理的外周血单核细胞(OGD-PBMCs)是缺血性中风的治疗策略。在这里,体外鉴定 OGD-PBMCs 分泌重塑因子,包括血管内皮生长因子和转化生长因子-β,而在局灶性脑缺血后 7 天经动脉内给予 OGD-PBMCs 可促使在体内局灶性脑缺血后 28 天脑实质中表达这些因子。此外,给予 OGD-PBMCs 可在体外和体内诱导越来越多的阶段特异性胚胎抗原-3 阳性细胞。最后,发现它可促进血管生成和轴突生长,以及脑缺血后的功能恢复。总之,给予 OGD-PBMCs 可能是一种针对缺血性中风的新的治疗策略。