Remyelination is the process by which the central nervous system (CNS) repairs itself after damage to the myelin sheath, the insulating material that covers and protects nerve cells. The myelin sheath is composed of lipids and proteins, and it acts as an electrical insulator, keeping neuronal impulses tightly regulated. When this protective covering is damaged, it can result in a number of neurological disorders, including multiple sclerosis (MS), cerebral palsy, and spinal cord injury. Remyelination is a complex process that involves both the regeneration of new myelin sheaths as well as the repair of existing ones. It is thought to be mediated by oligodendrocytes, specialized cells in the CNS that produce myelin.
There are several stages to remyelination: first, oligodendrocyte progenitor cells (OPCs) must migrate to the site of demyelination; next, these OPCs must differentiate into mature oligodendrocytes; finally, these newly-formed oligodendrocytes must extend their processes and wrap them around axons to form new myelin sheaths. This last stage is particularly challenging because it requires coordination between numerous cell types; if any one step goes awry, remyelination may be incomplete or fail entirely.
Despite its importance, our understanding of remyelination remains quite limited. In part this reflects technical difficulties: unlike other cell types in the CNS, oligodendrocytes are relatively rare and difficult to study in vivo. Additionally, current animal models of demyelinating disease do not perfectly recapitulate human disease progression; therefore it has been difficult to directly translate findings from animal studies into clinical therapies for humans. However, recent advances in stem cell research have created new opportunities for studying oligodendrogenesis and testing potential treatments for demyelinating diseases. Additionally, ongoing clinical trials are beginning to provide insights into how best to promote remyelination in patients with MS and other disorders.
There are many unanswered questions about remyelination still waiting to be explored: What factors determine whether or not an OPC will successfully differentiate into an oligodendrocyte? How does axonal architecture influence where new myelin sheaths are formed? Can we harness endogenous repair mechanisms to promote more complete remyelination? Answers to these questions will improve our understanding of normal CNS development and function as well as provide clues about how best to treat patients with demyelingating diseases.