神经干细胞(NSC)迄今是治疗神经损伤和神经退变性疾病最具有应用前景的细胞，然而NSC来源严重匮乏等诸多问题使其成为神经再生医学应用的瓶颈。因此寻求理想的替代细胞显得尤为重要。基于我们前期研究，嗅鞘细胞(OEC)和Shh、FGF8a、TGFβ3 等因子能协同诱导小鼠精原干细胞(SSC)系转分化为功能性多巴胺(DA）神经元。本项目以人的SSC为切入点，采用OEC合并限定性生长因子诱导使其转化为DA神经元。从形态特征和生化表型对产生的DA神经元进行鉴定，进一步检测并评估它的体外和在体功能，拟建立高效诱导人SSC转分化为功能性DA神经元的技术平台，为临床上帕金森等神经退变性疾病的细胞治疗和组织工程提供重要的细胞来源和新的思路。目前SSC转分化的分子机制尚不清楚。本项目将探明SSC直接分化为功能性DA神经元的PI3K/AKT和Smad1/5/8信号转导通路，为阐释SSC跨谱系分化提供新的分子机理。

Neural stem cells (NSCs) are hitherto regard as powerful perspective candidates for cell transplantation in clinical therapies for multilevel neural injury and degenerative diseases. However,the extreme shortage of NSCs available for transplantation still makes its therapeutic application a significant bottleneck in neural regenerative medicine.Therefore it is pivotal solution to seek an ideal cellular pool, which offers an alternative to further overcome the issue. Fascinatingly, Our recent studies evidenced that spermatogonial stem cell(SSC) line could transdifferentiate into DAergic(DA) neuronal cells under a special condition, namely a combination of olfactory enseathing cells(OECs) and defined factors such as GDNF, Shh, TGFβ3 and FGF8a, suggesting that SSCs could potentially become an acceptable alternative cellular resource. On the basis of this result, The aims of our present project are to systematically investigate transdifferentiation of human spermatogonial stem cells to DA neurons, to further optimize these protocols for the generation of DA neurons from SSCs to establish an efficient technology platform. Meanwhile, SSCs derived DA neurons were identified by means of the morphological characteristics and biochemical phenotypies. Concomitantly, the assessement of DA neurons in vitro and in vivo physiological functions was also conducted. We will eventually develop an effective strategy for transdifferentiation of human SSCs to DA neurons, which could contribute immensely to clinical applications of SSCs as a novel alternative to current neural stem cell source in treating PD, and also provide an alternative therapeutic solution for neural degenerative diseases. Furthermore, up to date an effort still remains in understanding of the molecular mechanisms underlying neural transdifferentiation of SSCs. Thus, the present study will be undertaken to further elucidate the molecular mechanism by which SSCs directly transdifferentiate into functional DA neurons through PI3K/AKT and Smad1/5/8 signaling pathways.It may provide noval theoretical basis for clarification of the molecular mechanism of SSCs transdifferentiation.