2019.11.18
A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation
（Sci Rep. 2019 Nov 14;9(1):16819. doi: 10.1038/s41598-019-53418-5.）
Hatakeyama M1, Kanazawa M2, Ninomiya I2, Omae K3, Kimura Y3, Takahashi T2, Onodera O2, Fukushima M3, Shimohata T4.
1Department of Neurology, Brain Research Institute, Niigata University
2Department of Neurology, Brain Research Institute, Niigata University
3Translational Research Center for Medical Innovation, Foundation for Biomedical Research and Innovation at Kobe
4Department of Neurology, Gifu University Graduate School of Medicine
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.
