Abstract TP132: The Combination Therapy of Intravenous Mannitol and Hypoxic Preconditioned Stem Cells for Ischemic Stroke

Abstract

Introduction: Hypoxic preconditioning of stem cells is currently employed as a strategy to prepare stem cells for increased survival and engraftment in the host. Mannitol enhances blood-brain barrier permeabilization and can improves the efficiency of systemically administered stem cells. The aim of this study is to elucidate the neuroprotective effects of combination of intravenous mannitol injection and the preconditioned stem cell transplantation on stroke induced neural injury. Materials and Methods: Human adipose stem cells (hADSCs) and mouse induced neural stem cells (miNSCs) were subjected to hypoxic preconditioning by culture in 2% O 2 . 24 hours after middle cerebral artery occlusion, all experimental animals were injected with mannitol intravenously. Five or ten minutes after mannitol injection, vehicle (PBS) or normal hADSCs or preconditioned hADSCs or normal miNSCs or preconditioned miNSCs were intravenously administered to the stroke animals. Neurobehavior functions and infarction volume were compared among the experimental groups. Immunohistochemistry was also performed to reveal the stem cell migration into the brain and histological changes after stem cell implantation. Results: Mannitol injection 10 minutes before stem cell transplantation more increased cell permeability compared to that of 5 and 15 minutes (p<0.05). Hypoxic preconditioned hADSCs more improved neurobehavioral deficits compared to any other stem cell groups (p<0.001). Immunohistological studies showed that stem cell treatment increased neuronal proliferation and angiogenesis, and decreased inflammatory reaction. The combination therapy of mannitol and hypoxic preconditioned hADSCs showed more increased neuronal proliferation and angiogenesis compared to any other stem cell groups (p<0.01). Conclusion: Based on our data, the combination therapy of mannitol and hypoxic preconditioned stem cells seems to have therapeutic potential for the ischemic stroke. Furthermore, hypoxic preconditioned hADSCs more augmented neuronal proliferation compared to normal hADSCs and preconditioned miNSCs. These findings suggest that hADSCs might be more eligible to hypoxic preconditioning than iNSCs for ischemic stroke.