A novel therapeutic approach using peripheral blood mononuclear cells preconditioned by oxygen-glucose deprivation.
Masahiro HatakeyamaMasato KanazawaItaru NinomiyaKaoru OmaeYasuko KimuraTetsuya TakahashiOsamu OnoderaMasanori FukushimaTakayoshi ShimohataPublished in: Scientific reports (2019)
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.
Keyphrases
- cerebral ischemia
- subarachnoid hemorrhage
- vascular endothelial growth factor
- blood brain barrier
- brain injury
- transforming growth factor
- atrial fibrillation
- blood glucose
- endothelial cells
- epithelial mesenchymal transition
- induced apoptosis
- poor prognosis
- single cell
- spinal cord injury
- inflammatory response
- mesenchymal stem cells
- high glucose
- spinal cord
- diabetic rats
- skeletal muscle
- cell death
- cell therapy
- signaling pathway
- weight loss
- drug induced
- optical coherence tomography