Modelling large areas of demyelination in the rat reveals the potential and possible limitations of transplanted glial cells for remyelination in the CNS
Modelling large areas of demyelination in the rat reveals the potential and possible limitations of transplanted glial cells for remyelination in the CNS
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作者：
Blakemore, WF;Chari, DM;Crang, AJ
在内源性髓鞘再生失败的情况下，髓鞘形成胶质细胞的移植可能提供一种实现髓鞘再生的手段。为了使这种类型的细胞治疗成功，细胞必须在正常组织和脱髓鞘区域内长距离迁移。在这项研究中，使用40 Gy的x射线照射来消耗组织中的内源性少突胶质细胞祖细胞（OPCs）。通过将新生儿OPCs移植到opc缺失组织中，我们能够检测新生儿OPCs重新填充opc缺失组织的速度。利用NG-2蛋白多糖抗体和原位杂交技术检测血小板衍生生长因子α受体rα (pdgfrα) mRNA来可视化OPCs，我们能够证明新生儿OPCs比内源性OPCs更快地重新填充opc缺失的正常组织3-5倍。移植的新生儿OPCs可使OPC密度恢复到接近正常值，当移植的OPCs在1个月前植入的组织中形成脱髓鞘病变时，我们能够证明移植的细胞在融入宿主组织后仍具有强大的轴突再髓鞘化能力。为了模拟可能在人类中发生的大面积opc耗尽脱髓鞘区域中存在的情况；我们清除了其内源性OPC群体的组织，并将局灶性脱髓鞘病变放置在距离新生儿OPC来源（小于或等于1厘米）的地方。在这种情况下，细胞将不得不重新填充耗尽的组织，以达到脱髓鞘的区域。由于再生过程需要时间，该模型允许我们检查延迟OPCs和脱髓鞘轴突之间相互作用对再髓鞘形成的影响。通过这种方法，我们获得的数据表明，延迟OPCs与脱髓鞘轴突之间相互作用的时间限制了移植OPCs再髓鞘潜能的表达。科学通报，2002。(C) 2002 Wiley-Liss, Inc。
Transplantation of myelin-forming glial cells may provide a means of achieving remyelination in situations in which endogenous remyelination fails. For this type of cell therapy to be successful, cells will have to migrate long distances in normal tissue and within areas of demyelination. In this study, 40 Gy of X-irradiation was used to deplete tissue of endogenous oligodendrocyte progenitors (OPCs). By transplanting neonatal OPCs into OPC-depleted tissue, we were able to examine the speed with which neonatal OPCs repopulate OPC-depleted tissue. Using antibodies to NG-2 proteoglycan and in situ hybridisation to detect platelet-derived growth factor alpha-receptor Ralpha (PDGFRalpha) mRNA to visualise OPCs, we were able to show that neonatal OPCs repopulate OPC-depleted normal tissue 3-5 times more rapidly than endogenous OPCs. Transplanted neonatal OPCs restore OPC densities to near-normal values and when demyelinating lesions were made in tissue into which transplanted OPCs had been incorporated 1 month previously, we were able to show that the transplanted cells retain a robust ability to remyelinate axons after their integration into host tissue. In order to model the situation that would exist in a large OPC-depleted area of demyelination such as may occur in humans; we depleted tissue of its endogenous OPC population and placed focal demyelinating lesions at a distance (less than or equal to1 cm) from a source of neonatal OPCs. In this situation, cells would have to repopulate depleted tissue in order to reach the area of demyelination. As the repopulation process would take time, this model allowed us to examine the consequences of delaying the interaction between OPCs and demyelinated axons on remyelination. Using this approach, we have obtained data that suggest that delaying the time of the interaction between OPCs and demyelinated axons restricts the expression of the remyelinating potential of transplanted OPCs. GLIA 38:155-168, 2002. (C) 2002 Wiley-Liss, Inc.