GLIAL-CELL TRANSPLANTS THAT ARE SUBSEQUENTLY REJECTED CAN BE USED TO INFLUENCE REGENERATION OF GLIAL-CELL ENVIRONMENTS IN THE CNS

Transplantation of glial cells into demyelinating lesions in CNS offer s an experimental approach which allows investigation of the complex i nteractions that occur between CNS glia, Schwann cells, and axons duri ng remyelination and repair. Earlier studies have shown that 1) transp lanted astrocytes are able to prevent Schwann cells from participating in CNS remyelination, but that they are only able to do so with the c ooperation of cells of the oligodendrocyte lineage, and 2) transplante d mouse oligodendrocytes can remyelinate rat axons provided their reje ction is controlled by immunosuppression. On the basis of these observ ations, we have been able to prevent the Schwann cell remyelination th at normally follows ethidium bromide demyelination in the rat spinal c ord by co-transplanting isogeneic astrocytes with a potentially reject able population of mouse oligodendrocyte lineage cells. Since male mou se cells were used it was possible to demonstrate their presence in im munosuppressed recipients using a mouse Y-chromosome probe by in situ hydridisation. When myelinating mouse cells were rejected by removal o f 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 oligo dendrocyte 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-irrad iation, the lesion consisted of demyelinated axons surrounded by proce sses from the transplanted astrocytes. By this approach, it was possib le to create an environment which resembled the chronic plaques of mul tiple sclerosis. Thus, these experiments demonstrate that in appropria te circumstances the temporary presence of a population of glial cells can alter the outcome of damage to the CNS. (C) 1995 Wiley-Liss, Inc.