Cell reprogramming for oligodendrocytes: A review of protocols and their applications to disease modeling and cell-based remyelination therapies.

Abstract

Oligodendrocytes are a type of glial cells that produce a lipid-rich membrane called myelin. Myelin assembles into a sheath and lines neuronal axons in the brain and spinal cord to insulate them. This not only increases the speed and efficiency of nerve signal transduction but also protects the axons from damage and degradation, which could trigger neuronal cell death. Demyelination, which is caused by a loss of myelin and oligodendrocytes, is a prominent feature of many neurological conditions, including Multiple sclerosis (MS), spinal cord injuries (SCI), and leukodystrophies. Demyelination is followed by a time of remyelination mediated by the recruitment of endogenous oligodendrocyte precursor cells, their migration to the injury site, and differentiation into myelin-producing oligodendrocytes. Unfortunately, endogenous remyelination is not sufficient to overcome demyelination, which explains why there are to date no regenerative-based treatments for MS, SCI, or leukodystrophies. To better understand the role of oligodendrocytes and develop cell-based remyelination therapies, human oligodendrocytes have been derived from somatic cells using cell reprogramming. This review will detail the different cell reprogramming methods that have been developed to generate human oligodendrocytes and their applications to disease modeling and cell-based remyelination therapies. Recent developments in the field have seen the derivation of brain organoids from pluripotent stem cells, and protocols have been devised to incorporate oligodendrocytes within the organoids, which will also be reviewed.