Nascent glial precursors in human bone marrow allow rapid induction of functional oligodendrocyte precursors for therapy

Loss of myelinating oligodendrocytes and myelin in white matter diseases impacts motor and cognitive functions, and even life expectancy. Transplantation of autologous oligodendrocyte precursors (OPCs) hold promise for treatment of such diseases, but a protocol for rapid generation of human OPCs from safe, ethical and accessible cell source remains unfound. We pursued strategies whereby rat bone marrow stromal cells (BMSCs) could be differentiated into myelinating glia of both the central and peripheral nervous system (1). By source, it remains unknown clinically collected human BMSCs (hBMSCs) could differentiate into OPCs, with good purity and yield. Furthermore, whether the multipotency of BMSCs resulted from diverse progenitors pre-existing in the bone marrow or from a single multipotent progenitor population remained unaddressed. hBMSCs collected from 3 healthy individuals were sequenced at single cell level and featured a transcriptomically distinct population of CD90hiEGFR+PDGFRA+ pre-oligodendrocyte precursors cells (pre-OPCs). To achieve targeted expansion of this population a two-step, virus-free and supporting cell-free induction protocol was designed and implemented. This was sufficient to derive immature-OPCs from hBMSCs. Transcriptomes of these immature-OPCs were characterized by single cell sequencing and their marker expression was examined by immunostaining. Transplantation into myelin-deficient shiverer mice was used to demonstrate that our derived cells were capable of myelinating naked axons. Immature-OPCs were derived from hBMSCs in eight days using a simple two-step protocol. Resulting cells were positive for OPC markers and capable of myelinating naked axons when transplanted into the corpus callosum of myelin-deficient Shiverer mice. Our results provide evidence that hBMSCs harbour multipotent pre-OPCs, that features inherent diversity in lineage-restricted progenitors pre-existing in the bone marrow. We show that one such progenitor pool can be selectively enriched and maturated harnessing protocols to yield highly pure fate-committed oligodendrocytes. This could address myelin deficiency due to autoimmune, degenerative and traumatic conditions of the central nervous system.