Franklin R J, Bayley S A, Blakemore W F
Department of Clinical Veterinary Medicine and MRC Cambridge Centre for Brain Repair, University of Cambridge, United Kingdom.
Exp Neurol. 1996 Feb;137(2):263-76. doi: 10.1006/exnr.1996.0025.
In this study, we have examined the behavior of a lac-Z-transfected O- 2A progenitor cell line, CG4, following transplantation into normal and X-irradiated adult rat spinal cord, and we have also addressed the issue of whether CG4 cells transplanted remotely from ethidium bromide-induced demyelinating lesions in both X-irradiated and nonirradiated spinal cord are able to contribute to their repair. Following transplantation into X-irradiated spinal cord, CG4 cells survive, divide, and migrate extensively. The migration occurs mainly within the parenchymal tissue of the cord without preference for white or gray matter. Moreover, CG4 cells migrating away from their point of introduction are able to enter areas of demyelination and remyelinate the demyelinated axons therein. In contrast, when CG4 cells are transplanted into nonirradiated spinal cord, their survival is limited to areas of damage created by the injection procedure. The CG4 cells do not survive in undamaged, nonirradiated spinal cord. When transplanted remotely from areas of demyelination they are unable to traverse intervening areas of normal white matter, although they may enter lesions if transplanted into their close vicinity. These results have important implications for the development of potential therapeutic strategies for the treatment of multifocal demyelinating disorders that are based on glial cell transplantation.
在本研究中,我们检测了经β-半乳糖苷酶转染的少突胶质细胞-2A祖细胞系CG4在移植到正常和经X射线照射的成年大鼠脊髓后的行为,并且我们还探讨了在经X射线照射和未照射的脊髓中,从溴化乙锭诱导的脱髓鞘损伤处远距离移植的CG4细胞是否能够促进损伤修复这一问题。移植到经X射线照射的脊髓后,CG4细胞存活、分裂并广泛迁移。迁移主要发生在脊髓实质组织内,对白质或灰质无偏好。此外,从引入点迁移离开的CG4细胞能够进入脱髓鞘区域并对其中的脱髓鞘轴突进行髓鞘再生。相比之下,当CG4细胞移植到未照射的脊髓中时,它们的存活仅限于注射操作造成的损伤区域。CG4细胞在未受损、未照射的脊髓中无法存活。当从脱髓鞘区域远距离移植时,它们无法穿过正常白质的中间区域,尽管如果移植到其附近区域,它们可能会进入损伤部位。这些结果对于基于胶质细胞移植治疗多灶性脱髓鞘疾病的潜在治疗策略的开发具有重要意义。