Specific induction of Schwann cells, neurons and skeletal muscle cells from bone marrow stromal cells and application for degenerative diseases

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 Bone marrow stromal cells (MSCs). Schwann cells is known to support axonal elongation. MSCs treated with beta‐mercaptoethanol followed by retinoic acid (RA) and cytokines expressed markers of Schwann cells. They promoted axonal regeneration and functional recovery when transplanted into the spinal cord injury rat model. Neuronal induction could be achieved by Notch intracellular domain (NICD) transfection followed by trophic factor administration. Induced cells consisted of post‐mitotic fiunctional neurons without differentiation of glial cells. 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 which is beneficial to neuro‐ and muscle‐degenerative diseases.