人诱导多能干细胞衍生的少突胶质细胞祖细胞治疗缺血性脑损伤的研究

Stroke is the leading cause of death and disability in the world. At present, there is lack of effective treatment methods in the world as well as in China. White matter injury is an important pathological change in the vast majority of stroke, manifested as oligodendrocytes (OL) injury, nerve demyelination, and loss of nerve axon. During the stroke recovery, the brain cannot supply enough oligodendrocyte progenitor cells (OPC) to produce OL and form myelin. Therefore, providing exogenous OPC for generation of new OL and sufficient myelin sheaths on restoration of the structure and function of neurons and their axons may be a new hoep for the treatment of ischemic stroke. Previously, we have achieved significant efficacy on the treatment of rodent demyelinating lesions using hiPSC induced OPC. We have mastered a set of techniques for identification, isolation and transplantation of hiPSC induced OPC. On this basis, we hypothesize whether hiPSC derived OPC can be used to treat white matter lesion in ischemic stroke in rodents? We will perform stereotaxic injection of hiPSC derived OPC to the area of ischemic brain injury in mice. We will study in vivo process of OL generation and its myelination, as well as the possible mechanisms and effects of implanted OPC on functional improvement of injured neurons. We hope that the results of this study can provide a new method and idea for the treatment of ischemic stroke in human.

脑卒中是世界上人类死亡和残疾的首要原因。目前国内外缺稀有效的治疗方法。白质损伤是绝大多数脑卒中的重要病理变化，表现为少突胶质细胞(OL)损伤、神经脱髓鞘、及神经轴突丧失。在卒中恢复中，脑内不能提供足够的少突胶质细胞祖细胞(OPC)以产生OL并形成髓鞘。因此，提供外源性OPC产生新的OL和神经髓鞘以供神经轴突结构和功能恢复就可为治疗缺血性脑卒中的新希望。我们之前使用hiPSC诱导的OPC治疗啮齿类动物脱髓鞘病变取得显著疗效。我们掌握了一套鉴定、分离和移植hiPSC诱导的OPC的技术。在此基础上提出假设，hiPSC衍生的OPC能否用于治疗啮齿类动物缺血性脑卒中的白质损伤？我们将经脑立体定位注射hiPSC衍生的OPC到小鼠脑缺血损伤区，研究新生OL和髓鞘在体内形成过程及植入OPC对损伤神经元功能改善的可能机制和效果。我们期望本课题的研究成果能为缺血性脑卒中恢复期治疗提供新方法和新思路。

脑卒中是世界上人类死亡和残疾的首要原因。目前，国内外缺稀有效的根本治疗方法。白质损伤是绝大多数脑卒中的重要病理变化，表现为少突胶质细胞(OL)损伤、神经脱髓鞘、及神经轴突丧失。在卒中恢复中，脑内不能提供足够的少突胶质细胞祖细胞(OPC)以产生OL并形成髓鞘。因此，提供外源性OPC产生新的OL和神经髓鞘以供神经轴突结构和功能恢复就可为治疗缺血性脑卒中的新希望。我们之前使用hiPSC和hESC诱导的hOPC治疗啮齿类动物脱髓鞘病变取得显著疗效。在此基础上我们进一步改良优化了一套鉴定、分离和移植hiPSC和hESC诱导的hOPC的技术。我们经基因组学的方法进一步验证了新产生的hOPC的真实性。我们经脑立体定位注射这些hOPC到大鼠脑卒中缺血损伤区后，研究新生OL和髓鞘在大鼠脑内形成的过程及植入hOPC对损伤神经元功能改善的机制和效果,验证了hOPC能够用于治疗啮齿类动物缺血性脑卒中的白质损伤的可能性。本课题的研究成果可能为缺血性脑卒中恢复期治疗提供新方法和新思路。