Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.05.078642v1?rss=1 Authors: Mozafari, S., Starost, L., Manot-Saillet, B., Garcia-Diaz, B., Xu, Y. K. T., Roussel, D., Levy, M. J. F., Ottoboni, L., Kim, K.-P., Scholer, H. R., Kennedy, T. E., Antel, J. P., Martino, G., Angulo, M. C., Kuhlmann, T., Baron-Van Evercooren, A. Abstract: The 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 regulators of the oligodendroglial biology or reflect MS oligodendrocyte intrinsic properties. To avoid confounding immune-mediated extrinsic effect, we used an immune-deficient, dysmyelinating mouse model, to compare side-by-side induced pluripotent stem-cell-derived O4+ oligodendroglia from MS and healthy donors following their engraftment in the developing CNS. We show that the MS-progeny survives, proliferates and differentiates into oligodendrocytes to the same extent as controls. Quantitative multi-parametric imaging indicates that MS and control oligodendrocytes generate equal amounts of myelin, with bona-fide nodes of Ranvier and promote equal restoration of their host slow conduction. Moreover, the MS-derived progeny expressed oligodendrocyte- and astrocyte-specific connexins and established functional connections with donor and host glial cells. Thus, MS pluripotent stem cell-derived progeny fully integrates into functional axo-glial and glial-glial components, reinforcing the view that the MS oligodendrocyte differentiation block is not due to intrinsic oligodendroglial deficits. These biological findings as well as the fully integrated human-murine chimeric model should facilitate the development of pharmacological or cell-based therapies to promote CNS remyelination. Copy rights belong to original authors. Visit the link for more info