Schwann cells and their precursors for repair of central nervous system myelin

In multiple sclerosis (MS), axons of the central nervous system lose their myelin sheaths, and there is also death of oligodendrocytes. Although some demyelinated axons rebuild their membranes so that they can conduct action potentials in the absence of myelin insulation, others do not; and loss of the myelin thus impairs impulse conduction either temporarily or permanently. Mounting evidence also suggests that loss of central myelin may have the secondary consequence of making axons more sensitive to damage or may, in itself, produce changes that impair axonal integrity, thereby leading to cumulative loss of axons that culminates in irreversible neurological deficits (Waxman, 2006). While a number of treatments such as the beta interferons (IFN-β) and glatirimer acetate (GA) are now available for the treatment of MS, and clinical studies using autologous haematopoietic stem cell transplantation (HSCT) and monoclonal antibody interventions in MS patients have shown profound suppression of inflammatory activity in many patients, these interventions were developed in the attempt to mute the immune attack on the nervous system in MS, and not with the goal of repairing demyelination. Thus, even if the immune assault on the nervous system in MS could be halted by a new immuno-modulatory therapy and the subsequent cascade of tissue damage thereby stalled, hundreds of thousands of people harboring MS lesions would still be left with neurological deficits. It is therefore not surprising that myelin repair has become an area of major interest in MS research. Important progress in this respect has come from studies that have examined cell-based approaches to myelin repair.A critical issue for cell-based myelin repair is the choice of cell type for transplantation. The transplanted cell must be able to survive, migrate to demyelinated lesions, remyelinate axons and not be tumorogenic. Oligodendrocyte lineage cells, neural progenitor cells, post-natal Schwann cells, …