Development of new gel used for artificial nerve to differenciate neural stem cells and to promote elongation ofaxons in damaged peripheral and central nervous system

神经干细胞移植被广泛用于治疗中枢神经系统(CNS)损伤(Seaberg和van-der-Kooy，2002；Van-der-Kooy和Weiss，2000；Fuchs和Segre，2000)。移植有不同的方法，包括直接局部注射，使用或不使用人工底物作为细胞载体(Wu等人，2001年)到受伤的大脑(Fricker等人，1999；Gage等人，1995年)和脊髓(秋山等人，2001年)。另一方面，基因治疗剂(Bajocchi等人，1993)、神经营养因子(Araujo和Hilt，1997)和药物如尼替卡酮(Mannisto等人，1992)已经通过CSF被给予。我们观察了从第四脑室注射后长达3周的海马源性神经干细胞在脊髓表面的分布。注射的细胞在脊髓软脑膜上以微小斑点的形式扩散，并增殖成大的细胞团。在背侧和…上腹侧较多的细胞团在注射后5天内迅速增多，之后由于相邻细胞团的结合而逐渐减少。与此同时，单个细胞团的大小不断增大，几乎占据了脊髓表面的50%。细胞附着通常见于血管周围，细胞沿血管侵入脊髓。在损伤部位，细胞迁移到损伤处并整合到脊髓组织中，其中一些细胞在注射后1-2周已分化为星形胶质细胞。BrdU摄取实验表明，移植的细胞在宿主脑脊液中增殖。这些结果表明，通过脑室应用神经干细胞是一种独特的方法，将细胞传播到整个脊髓，并且它们可以迁移并整合到损伤的脊髓中。神经干细胞移植已被广泛研究用于治疗中枢神经系统(CNS)损伤(Seaberg和van-der-Kooy，2002；Van-der-Kooy和Weiss，2000；Fuchs和Segre，2000)。移植有不同的方法，包括直接局部注射，使用或不使用人工底物作为细胞载体(Wu等人，2001年)到受伤的大脑(Fricker等人，1999；Gage等人，1995年)和脊髓(秋山等人，2001年)。另一方面，基因治疗剂(Bajocchi等人，1993)、神经营养因子(Araujo和Hilt，1997)和尼替卡酮(Mannisto等人，1992)等药物已通过脑脊液给药。较少

Transplantation of neural stem cells has been studied extensively for the treatment of central nervous system(CNS) injury (Seaberg and van-der-Kooy,2002;Van-der-Kooy and Weiss, 2000;Fuchs and Segre,2000). There have been various approaches to transplantation, including direct local administration by injection with or without artificial substrates as cell carriers (Wu et al.,2001) into the injured brain (Fricker et al.,1999;Gage et al.,1995) and spinal cord (Akiyama et al.,2001). On the other hand, gene therapeutic agents (Bajocchi et al.,1993), neurotrophic factors (Araujo and Hilt,1997) and drugs such as nitecapone (Mannisto et al.,1992) have been administered through the CSF.We examined the distribution of hippocampus-derived neural stem cells on the spinal cord surface for up to 3 weeks following injection through the 4th ventricle. The injected cells were disseminated as tiny spots on the pia mater of the spinal cord and proliferated into large cell-clusters. On both the dorsal and … More ventral side, cell clusters increased in number rapidly up to 5 days after injection, and thereafter decreased gradually due to the coalition of neighbouring clusters. Concomitantly, individual cell clusters continuously increased in size, occupying almost 50% of the spinal cord surface. Cell attachment was usually found around blood vessels, along which cells invaded into the spinal cord. In the injured site, cells migrated into the lesion and were integrated into the spinal cord tissue, some of which had differentiated into astrocytes 1-2 weeks after injection. BrdU-uptake experiments demonstrated that the transplanted cells proliferated within the host cerebrospinal fruid.These results indicate that application of neural stem cells through the ventricle is a unique method to disseminate cells all over the spinal cord, and that they can migrate and be integrated into the injured spinal cord.Transplantation of neural stem cells has been studied extensively for the treatment of central nervous system(CNS) injury (Seaberg and van-der-Kooy,2002;Van-der-Kooy and Weiss, 2000;Fuchs and Segre,2000). There have been various approaches to transplantation, including direct local administration by injection with or without artificial substrates as cell carriers (Wu et al.,2001) into the injured brain (Fricker et al.,1999;Gage et al.,1995) and spinal cord (Akiyama et al.,2001). On the other hand, gene therapeutic agents (Bajocchi et al.,1993), neurotrophic factors (Araujo and Hilt,1997) and drugs such as nitecapone (Mannisto et al.,1992) have been administered through the CSF. Less