Survival and differentiation of Transplanted mouse embryonic stem cells in focal ischemic rat brain

Abstract

Background & Objectives : To assess the potential of embryonic stem cells to undergo neuronal differentiation in the ischemic brain of adult rats after middle cerebral artery occlusion and reperfusion. Method : 9 to 10-week-old male SD rats were subjected to 2 hours of middle cerebral artery occlusion by koizumi method. one days after middle cerebral artery occlusion, totipotent mouse embryonic stem cells (cell line B5) were transplanted into striatum and lateral ventricle. All recipients were injected cyclosporine A (10 mg/kg) one day before transplantation. The integration of donor cells was analyzed on morphological studies by immunohistochemistry and confocal microscopy performed 3 days to 8 weeks posttransplantation Results : A subpopulation of donor cells differentiated into various types of neural cells that were positive for the mouse-specific M6 antigen, which is known be expressed on mouse neurons as well as being positive for neuronal marker NeuN in 4 and 8 weeks after transplantation. Moreover, donor cells that were positive for neuronal precursor marker Nestin and the astroglial marker glial fibrillary acidic protein were observed in 4 and 8 weeks after transplantation. Conclusion : These results suggest that new neurons can be generated from transplanted mouse embryonic stem cells in the focal ischemic rat brain and these neurons can survive for at least 8 weeks. Together, these findings contribute to basic research regarding future transplantation strategies for brain repair after ischemic brain injury such as stroke.