Blakemore W F, Crang A J, Franklin R J, Tang K, Ryder S
MRC Cambridge Center for Brain Repair, University of Cambridge, United Kingdom.
Glia. 1995 Feb;13(2):79-91. doi: 10.1002/glia.440130202.
Transplantation of glial cells into demyelinating lesions in CNS offers an experimental approach which allows investigation of the complex interactions that occur between CNS glia, Schwann cells, and axons during remyelination and repair. Earlier studies have shown that 1) transplanted astrocytes are able to prevent Schwann cells from participating in CNS remyelination, but that they are only able to do so with the cooperation of cells of the oligodendrocyte lineage, and 2) transplanted mouse oligodendrocytes can remyelinate rat axons provided their rejection is controlled by immunosuppression. On the basis of these observations, we have been able to prevent the Schwann cell remyelination that normally follows ethidium bromide demyelination in the rat spinal cord by co-transplanting isogeneic astrocytes with a potentially rejectable population of mouse oligodendrocyte lineage cells. Since male mouse cells were used it was possible to demonstrate their presence in immunosuppressed recipients using a mouse Y-chromosome probe by in situ hydridisation. When myelinating mouse cells were rejected by removal of immunosuppression, the demyelinated axons were remyelinated by host oligodendrocytes rather than Schwann cells, whose entry was prevented by the persistence of the transplanted isogeneic astrocytes. The oligodendrocyte remyelination was extensive and rapid, indicating that the inflammation associated with cell rejection did not impede repair. If this host oligodendrocyte remyelination was prevented by local X-irradiation, the lesion consisted of demyelinated axons surrounded by processes from the transplanted astrocytes. By this approach, it was possible to create an environment which resembled the chronic plaques of multiple sclerosis. Thus, these experiments demonstrate that in appropriate circumstances the temporary presence of a population of glial cells can alter the outcome of damage to the CNS.
将神经胶质细胞移植到中枢神经系统的脱髓鞘损伤部位提供了一种实验方法，该方法能够研究在髓鞘再生和修复过程中，中枢神经系统胶质细胞、施万细胞和轴突之间发生的复杂相互作用。早期研究表明：1）移植的星形胶质细胞能够阻止施万细胞参与中枢神经系统的髓鞘再生，但只有在少突胶质细胞系细胞的协同作用下才能做到这一点；2）移植的小鼠少突胶质细胞能够使大鼠轴突重新髓鞘化，前提是通过免疫抑制来控制其排斥反应。基于这些观察结果，我们通过将同基因星形胶质细胞与具有潜在可排斥性的小鼠少突胶质细胞系细胞共同移植，成功阻止了大鼠脊髓中溴化乙锭脱髓鞘后通常会发生的施万细胞髓鞘再生。由于使用的是雄性小鼠细胞，因此可以通过原位杂交使用小鼠Y染色体探针在免疫抑制的受体中证明它们的存在。当通过去除免疫抑制使有髓鞘形成的小鼠细胞被排斥时，脱髓鞘的轴突由宿主少突胶质细胞而不是施万细胞重新髓鞘化，移植的同基因星形胶质细胞的持续存在阻止了施万细胞的进入。少突胶质细胞的髓鞘再生广泛且迅速，这表明与细胞排斥相关的炎症并未阻碍修复。如果通过局部X射线照射阻止这种宿主少突胶质细胞的髓鞘再生，损伤部位则由脱髓鞘的轴突和移植的星形胶质细胞的突起包围。通过这种方法，可以创造出一种类似于多发性硬化症慢性斑块的环境。因此，这些实验表明，在适当的情况下，一群神经胶质细胞的暂时存在可以改变中枢神经系统损伤的结果。
