Specific induction of functional neurons and skeletal muscle cells from bone marrow stromal cells and their application for auto-cell transplantation therapy in neuro-and muscle degenerative diseases

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Bone marrow stromal cells (MSCs) have the capability under specific conditions to differentiate into various cell types, such as osteocytes, chondrocytes and adipocytes. Here we demonstrate a highly efficient and specific induction of Schwann cells (peripheral glial cells), neurons and skeletal muscle cells from both rat and human MSCs.Neuronal induction could be achieved by NICD transfection followed by trophic factor administration of bFGF+ CNTF + forskolin. MSCs expressed markers related to neural stem cell and neuronal progenitor cells after transfection with NICD, and subsequent administration of trophic factors induced post-mitotic neurons without differentiation of glial cells. Some of induced cells showed action potentials compatible with characteristics of functional neurons. Further treatment of the neurons with GDNF increased the proportion of dopamine-producing cells and transplantation of these neurons showed improvement in rat model of Parkinson's disease. Highly efficient skeletal muscle induction could also be achieved by the administration of a combination of cytokines followed by NICD transfection. Induced cells differentiate into muscle fibers upon transplantation into degenerated muscles. Since induced cells contained satellite-like cells, they contributed to subsequent regeneration upon repetitive damage without additional transplantation of cells.Since our induction system does not depend on a rare stem cell population, but can utilize the general population of MSCs which can be easily isolated and expanded, functional Schwann cells, neurons and skeletal muscle cells can be obtained on a therapeutic scale. Our MSC differentiation system may contribute substantially to a major advance toward eventual cell-based therapies for neurodegenerative and muscle degenerative diseases.