Functional recovery of the cerebral infarction following transplantation of the genetically-engineering human neural stem cells

虽然人们普遍认为，由于成年哺乳动物中枢神经系统（CNS）缺乏神经发生，成年哺乳动物的大脑无法进行显著的自我修复，但一些研究报道，在实验动物模型中，成年哺乳动物的大脑中含有神经干细胞，这些干细胞保留了神经产生和分化的潜力。这些发现为成人大脑中存在神经前体提供了前景。本研究的目的是鉴定成人中枢神经系统中的神经干细胞，并研究它们是否能修复缺血性脑。方法：体外培养成人脑源性神经干细胞。它们被遗传标记为LacZ基因，并被移植到实验动物的缺血脑中。观察移植后是否发生神经组织重建。结果：单细胞克隆分析表明，体外培养的成人大脑神经干细胞具有自我更新和多能性。移植后缺血病变的组织学检查显示移植的人细胞能重建神经组织。在对侧半球移植的干细胞也迁移到另一个半球的缺血性病变，并修复缺血应激后受损的大脑。电生理和行为学研究也证实了人神经干细胞移植后缺血模型动物的功能恢复。结论：成人大脑中含有神经干细胞，具有神经生成和分化的潜能。成人脑源性克隆神经干细胞移植修复哺乳动物成年中枢神经系统缺血神经组织。

Introduction: Although it has generally been assumed that the adult brain is incapable of significant self-repair because of a lack of neurogenesis in the adult mammalian central nervous system (CNS), several studies have reported that the adult mammalian brain harbors neural stem cells that retain the potential for both neural production and differentiation in experimental animal models. These findings offer the prospect of the presence of neural precursors in the adult human brain. The objective of this study was to identify neural stem cells in the adult human CNS and study whether they repair the ischemic brain.Methdos: Clonal neural stem cells derived from adult human brain were established in vitro. They were genetically marked with LacZ gene and was transplanted into the ischemic brain of the experimental animal. It was investigated if neural tissue reconstruction occurred following transplantation.Results: Single-cell clonal analysis demonstrated self-renewing and multipotential properties of neural stem cells derived from the adult human brain in vitro. Histological examination of the ischemic lesion following transplantation revealed that the transplanted human cells reconstructed the neural tissue. The transplanted stem cell in the contra-lateral hemisphere also migrated into the ischemic lesion of the another hemisphere, and repaired the damaged brain following ischemic stress. The electrophysiological and behavior studies also proved the functional recovery of the ischemic model animals following the human neural stem cell transplantation.Conclusion: Adult human brain harbors neural stem cells that retain the potential for both neural production and differentiation. Transplantation of clonal neural stem cells derived from adult human brain repaired the ischemic neural tissue in the mammalian adult CNS.