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 (< or =1 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.

中文翻译：

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对大鼠大面积的脱髓鞘进行建模，揭示了移植的神经胶质细胞在中枢神经系统中重新髓鞘化的潜力和可能的局限性。

在内源性髓鞘再生失败的情况下，形成髓磷脂的神经胶质细胞的移植可提供实现髓鞘再生的手段。为了使这种类型的细胞疗法成功，细胞将必须在正常组织中和脱髓鞘区域内长距离迁移。在这项研究中，使用40 Gy的X射线来消耗内源性少突胶质祖细胞（OPC）的组织。通过将新生儿OPC移植到OPC耗尽的组织中，我们能够检查新生儿OPC填充OPC耗尽组织的速度。使用针对NG-2蛋白聚糖的抗体和原位杂交技术检测血小板衍生的生长因子α受体Ralpha（PDGFRalpha）mRNA以可视化OPC，我们能够证明新生儿OPC可以使OPC耗尽的正常组织重新繁殖的速度快3-5倍。而不是内源性OPC。移植的新生儿OPCs使OPC密度恢复到接近正常值，并且在1个月前已植入移植OPCs的组织中形成脱髓鞘病变时，我们能够证明移植细胞整合入轴突后仍具有强大的髓鞘再生能力宿主组织。为了模拟OPC耗尽的大面积脱髓鞘情况（例如人类可能发生的情况）的情况；我们耗尽了其内源性OPC种群的组织，并将局灶性脱髓鞘病变置于距新生儿OPC来源一定距离（<或= 1 cm）的位置。在这种情况下，细胞必须重新填充耗尽的组织才能到达脱髓鞘区域。由于重新填充过程需要时间，该模型使我们能够研究延迟OPC和脱髓鞘轴突之间重新髓鞘作用的后果。使用这种方法，我们获得的数据表明，延迟OPC与脱髓鞘轴突之间的相互作用时间会限制已移植OPC的重新髓鞘表达。