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

开发用于人工神经的新型凝胶，以分化神经干细胞并促进受损外周和中枢神经系统的轴突伸长

基本信息

批准号：
14207073
负责人：
SUZUKI Yoshihisa
金额：
$ 32.28万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

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

已经对神经干细胞的移植进行了广泛的研究，以治疗中枢神经系统（CNS）损伤（Seaberg and van-der-Kooy，2002; van-der-kooy and Weiss，2000; Fuchs and Segre，2000）。有各种各样的移植方法，包括通过有或没有人工底物作为细胞载体的注射直接局部给药（Wu等，2001）进入受伤的大脑（Fricker等，1999; Gage等，1995）和脊髓（Akiyama等，2001）。另一方面，基因治疗剂（Bajocchi等，1993），神经营养因素（Araujo和Hilt，1997）和氮Capone（Mannisto等，1992）（1997年）（Mannisto et al。，1992）通过CSF进行了施用。我们通过CSF进行了三周的跨度神经孔的分布。心室。将注射的细胞传播为脊髓的PIA材料上的微小斑点，并扩散到大细胞群中。在背侧和……更腹侧，细胞簇的数量迅速增加到注射后5天，此后由于邻近群集的联盟逐渐减少。同时，单个细胞簇的大小继续增加，占据了近50％的脊髓表面。通常在血管周围发现细胞附着，细胞入侵脊髓。在受伤的部位，细胞迁移到病变中并整合到脊髓组织中，其中一些细胞在注射后1-2周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，通过通风应用神经元干细胞是一种将细胞在整个脊髓上传播的独特方法，它们可以迁移并整合到受伤的脊髓中。已经对神经干细胞的转移进行了广泛的研究，以治疗中枢神经系统（CNS和VAN-der-der-der-kooy，2000 and van-kooy，van-kooy，2000 and van-koy and fan-kooy，van-koy，van-koy and fan-kooy and fan-van-koy and fan-kooy and fan-kooy and fan-van-koy and fan and van-koy and van-koy and fan and-koy and fan and; Segre，2000年）。有各种各样的移植方法，包括通过有或没有人工底物作为细胞载体的注射直接局部给药（Wu等，2001）进入受伤的大脑（Fricker等，1999; Gage等，1995）和脊髓（Akiyama等，2001）。另一方面，基因治疗剂（Bajocchi等，1993），神经营养因子（Araujo和Hilt，1997）和Nitecapone（Mannisto等，1992）等药物已通过CSF施用。较少的