Directed Differentiation of Human Bone Marrow Stromal Cells to Fate-Committed Schwann Cells

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Abstract

Our ultimate goal of in vitro derivation of Schwann cells (SCs) from adult bone marrow stromal cells (BMSCs) is such that they may be used autologously to assist post-traumatic nerve regeneration. Existing protocols for derivation of SC-like cells from BMSCs fall short in the stability of the acquired phenotype and the functional capacity to myelinate axons. Our experiments indicated that neuro-ectodermal progenitor cells among the human hBMSCs could be selectively expanded and then induced to differentiate into SC-like cells. Co-culture of the SC-like cells with embryonic dorsal root ganglion neurons facilitated contact-mediated signaling that accomplished the switch to fate-committed SCs. Microarray analysis and in vitro myelination provided evidence that the human BMSC-derived SCs were functionally mature. This was reinforced by repair and myelination phenotypes observable in vivo with the derived SCs seeded into a nerve guide as an implant across a critical gap in a rat model of sciatic nerve injury. Ying-Shing Chan and colleagues demonstrate that the human bone marrow harbors neuro-ectodermal progenitors that can be enriched, expanded, and directed to differentiate into functionally mature, fate-committed SCs. This work holds promise for further development into an autologous cell source for implantation as a treatment strategy for nerve injuries or peripheral neuropathies.

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Cai, S., Tsui, Y. P., Tam, K. W., Shea, G. K. H., Chang, R. S. K., Ao, Q., … Chan, Y. S. (2017). Directed Differentiation of Human Bone Marrow Stromal Cells to Fate-Committed Schwann Cells. Stem Cell Reports, 9(4), 1097–1108. https://doi.org/10.1016/j.stemcr.2017.08.004

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