神经干细胞（NSC）目前是治疗脊髓损伤实现功能恢复最具有应用前景的细胞，然而NSC来源匮乏及伦理等诸多问题使其成为再生医学应用的瓶颈。因此找寻最佳的替代细胞尤为重要。基于我们前期研究，GDNF修饰的嗅鞘细胞(OEC)和RA、IBMX等小分子能有效地诱导大鼠精原干细胞(SSC)及C18-4细胞系转分化为脊髓神经元。本项目拟以大鼠SSC为切入点，采用GDNF修饰的OEC联合限定性小分子诱导其转分化为脊髓神经元。从细胞形态特征和生化表型对产生的脊髓神经元进行鉴定,进一步对其体外和在体生物功能进行检测和评估，拟建立高效诱导SSC转分化为功能性脊髓神经元的技术平台，为临床上应用细胞治疗脊髓损伤和组织工程提供重要的细胞来源及新思路。迄今SSC转分化为神经元的分子机制尚不清楚。本项目将探究SSC直接分化为功能性脊髓神经元的PI3K-Wnt/Smad信号转导通路，为阐明SSC跨谱系分化提供新的分子机制。

Neural stem cells (NSCs) are hitherto regard as powerful perspective candidates for cell transplantation in clinical therapies for multilevel spinal cord injury and fucntion restoration. 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 reservoir as an alternative to further overcome the above-mentioned issue. Fascinatingly, Our recent studies evidenced that spermatogonial stem cells(SSCs) and C18-4 cells （SSC cell line） could transdifferentiate into spinal cord (SC) neural cells under a special condition, namely a combination of GDNF -modifed olfactory enseathing cells(OECs) and defined bio-active molecules such as RA, IBMX and TGFβ3, etc, 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 rat SSCs to SC neurons, to further screen most optimal approach for the generation of SC from SSCs to establish an efficient technology platform. Meanwhile, SSCs derived SC neurons were identified by means of the morphological characteristics and biochemical phenotypies. Concomitantly, the assessement of SC neurons in vitro and in vivo physiological functions was also conducted. We will eventually develop an effective strategy for transdifferentiation of rat SSCs to SC neurons, which could contribute immensely to clinical applications of SSCs as a novel alternative to current NSC source in treating SCI, and also provide an alternative therapeutic solution for neural degenerative diseases. Furthermore, up till now 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 possible molecular mechanism by which SSCs directly transdifferentiate into functional SC neurons through PI3K-Wnt/Catenin and Smad1/5/8 signaling pathways.This present project may provide noval theoretical basis for clarification of the molecular mechanism of SSCs transdifferentiation.