Nascent Glial Precursors in Human Bone Marrow Allow Rapid Induction of Functional Oligodendrocyte Precursors for...

Loss of myelinating oligodendrocytes and myelin impairs motor and cognitive functions. Transplantation of autologous oligodendrocyte precursors (OPCs) holds promise for treatment of such diseases, but a protocol to derive human OPCs from a safe, ethical and accessible cell source with the rapidity required to catch the therapeutic window remains to be found. Although we previously generated myelinating glia from rat bone marrow stromal cells (BMSCs), it remains unknown if clinically sourced human BMSCs (hBMSCs) share the same potential. Moreover, whether the multipotency of BMSCs results from diverse progenitors preexisting in the bone marrow or from a single multipotent progenitor population remains unaddressed. Single-cell RNA sequencing data revealed a CD90^hiEGFR⁺PDGFRA⁺ pre-OPC-like subpopulation within hBMSCs. With a small-molecule-based (virus-free and supporting-cell-free) two-step induction protocol designed to expand this pre-OPC population, we generated functional OPCs with high purity in eight days. These derived OPCs showed phenotypic transcriptomes and immunoprofiles. They were also capable of myelinating naked axons when transplanted into myelin-deficient shiverer mice. Results highlight how targeted enrichment and maturation of specific progenitor subpopulations within hBMSCs allows rapid induction of desired cell types. These results place hBMSCs as a robust source of OPCs, unlocking the possibility for cell transplantation therapy for myelin deficiency in the central nervous system.