The biology of the transplanted oligodendrocyte progenitor

Abstract

An important advance in oligodendrocyte biology during the 1980’s was the development of models and techniques for studying the myelinogenic capacity of transplanted glia (8). Two basic models emerged from which our current knowledge regarding the ability of transplanted glia to myelinate host axons is largely derived. The first of these are the so-called “myelin-mutants”, where a defect in one of the genes encoding central myelin proteins (such as the MBPmutant shiverer mouse, or the PLP-mutant myelin-deficient rat) gives rise to a hypomyelinated CNS containing abundant unmyelinated or demyelinated axons available for myelination by transplanted cells. In general, the myelin mutants are short-lived, and most studies using these animals have been undertaken in neonatal or immature recipients (7,14,21). The second transplantation model involves the creation of clearly-defined, focal areas of demyelination within the white matter of adult animals by the direct injection of small volumes of gliotoxic agents such as lysolecithin or ethidium bromide. The normally-occurring, spontaneous remyelination of gliotoxin-induced areas of demyelination can be prevented by exposing the lesion area to 40 Grays of X-irradiation, thereby creating a non-repairing area of demyelination (the X-EB lesion) with which to test the behaviour of transplanted cells in the absence of competition from recruited host cells (fig.la). The ability of transplants containing cells of the oligodendrocyte lineage to myelinate host axons was clearly demonstrated using both these models.