诱导多功能干细胞（iPSC）和诱导神经元（iN）的出现提示了也许可以直接将体细胞重编程为神经干细胞（iNSC）。iNSCs可以源于病人自身，所以不存在伦理及免疫排斥的问题，为治疗退行性神经系统疾病开辟了新的途径。我们在前期工作中成功的将小鼠的体细胞通过转入外源因子诱导成神经干细胞；这种iNSCs 可以在体外分化成具有电生理活性的成熟神经元并在移植到小鼠脑内后能够存活并向神经元分化。在申报的课题中，我们将延续这一工作，尝试将人和猴的皮肤细胞通过转入可调控的外源因子，诱导成有功能的iNSCs。在完成一系列的体外和体内鉴定以及因子组合优化的实验后，我们还会在免疫缺陷小鼠的帕金森模型和食蟹猴的帕金森模型中分别验证人源和猴源的iNSC的安全性和有效性。

The reports of induced pluripotent stem cells (iPSCs) and induced mature neurons (iNs) suggest a possibility to directly reprogram somatic cells into induced neural stem cells (iNSCs). Patient-specific iNSCs may open an avenue to the treatment of neurodegenerative diseases, in that iNSCs may circumvent the ethical issues and immune rejection problems. In our previous work, we have successfully converted murine somatic cells into iNSCs by defined factors; the murine iNSCs can differentiate to electrophysiologically functional mature neurons in vitro and survive transplantation into mouse brains and further turn into mature neurons in vivo. In the current proposal, we will extend this work and attempt to reprogram human and cynomolgus monkey fibroblasts into functional iNSCs by using an inducible system to deliver exogenous factors. Following a series of in vitro and in vivo characterization experiments, we will continue to test the safety and efficacy of human and monkey iNSCs in mouse and cynomolgus Parkinson's disease models, respectively.