A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation

一种利用氧葡萄糖剥夺预处理的外周血单核细胞的新型治疗方法

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作者:Masahiro Hatakeyama, Masato Kanazawa, Itaru Ninomiya, Kaoru Omae, Yasuko Kimura, Tetsuya Takahashi, Osamu Onodera, Masanori Fukushima, Takayoshi Shimohata

Abstract

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.

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