Remyelination failure in multiple sclerosis (MS) is associated with a migration/differentiation block of oligodendroglia. The reason for this block is highly debated. It could result from disease-related extrinsic or intrinsic
regulators in oligodendroglial biology. To avoid confounding immune-mediated extrinsic effect, we used an
immune-deficient mouse model to compare induced pluripotent stem cell–derived oligodendroglia from MS and
healthy donors following engraftment in the developing CNS. We show that the MS-progeny behaves and differentiates into oligodendrocytes to the same extent as controls. They generate equal amounts of myelin, with bona
fide nodes of Ranvier, and promote equal restoration of their host slow conduction. MS-progeny expressed
oligodendrocyte- and astrocyte-specific connexins and established functional connections with donor and host glia.
Thus, MS oligodendroglia, regardless of major immune manipulators, are intrinsically capable of myelination
and making functional axo-glia/glia-glia connections, reinforcing the view that the MS oligodendrocyte differentiation block is not from major intrinsic oligodendroglial deficits.
