Glial cell transplants: experimental therapies of myelin diseases

Abstract

Transplantation of cells into the CNS of human patients with neurodegenerative disorders offers a radical new approach to the treatment of previously incurable diseases. Considerable success has been achieved in Parkinson's disease following transplantation of human fetal dopaminergic neurons. Disorders of myelination of the brain, of either inherited or acquired origin, might also be treated by glial cell transplantation although there are additional challenges. Cells of the oligodendrocyte lineage have been found to be capable of myelinating axons on transplantation into numerous experimental pathological environments, including the CNS of myelin mutants and focal areas of demyelination in normal animals made by injection of myelinotoxic chemicals. In general, primary cells and progenitors are likely to have the greatest myelinating capacity. Cell lines can also be used, but those driven by oncogenes may produce little myelin, and tumor formation is likely. Schwann cells are also a potential source of cells, possibly as a homograft, and may be primed by treatment ex vivo with glial growth factors. The variable CNS milieu seen in human myelin disease will mean that transplanted cells must be able to migrate appropriately and myelinate axons in an adult, pathological environment, and this awaits experimental confirmation. Physiological analysis of transplants in such situations in adult animals will provide the functional data which may expedite clinical trials.