Derivation of human bone marrow-derived progenitor cells for remyelination therapy

Abstract

CNS myelination is facilitated by oligodendrocytes (OL). Disorders of myelin formation can be congenital or acquired and result in significant functional impairment. Congenital disorders of myelin formation are often fatal and pose as an attractive disease model for cell replacement therapy. We have previously been able to generate glia from rat and human bone marrow, as a means towards autologous cell therapy. In this study, we utilised our glial induction protocol to derive glial progenitor cells (GPCs) from bone marrow stromal cell (hBMSC) harvested from human diaphyseal marrow specimens. The generated hBMSC-GPCs were highly enriched in OPC markers expression, including OLIG-2, PDGFRα, NG2, SOX-10 and O4. Following transplantation into the myelin-deficient shiverer mouse brain, engrafted hBMSC-GPCs demonstrated the capacity for myelination as well as migration along white matter tracts. Both structural and functional rescue from hypomyelination was observed as hBMSC-OPC transplantation significantly extending mice lifespan, body weight, and motor function. No tumourogenicity was observed in mice sacrificed up to 5 months after transplantation. Our platform for generating myelinating glia from human bone marrow is rapid and efficient and promises a means of utilizing autologous cell therapy to treat demyelinating diseases and neurotrauma. Specifically, we circumvent hurdles to clinical translation associated with genetic reprogramming and narrow transplantation window periods.