Generation of phenotypically stable and functionally mature human bone marrow MSCs derived Schwann cells via the induction of human iPSCs-derived sensory neurons
Phenotypically unstable Schwann cell-like cells (SCLCs), derived from mesenchymal stem cells (MSCs) require intercellular contact-mediated cues for Schwann cell (SCs)-fate commitment. Although rat dorsal root ganglion (DRG) neurons provide contact-mediated signals for the conversion of SCLCs into fate-committed SCs, the use of animal cells is clinically unacceptable. To overcome this problem, we previously acquired human induced pluripotent stem cell-derived sensory neurons (hiPSC-dSNs) as surrogates of rat DRG neurons that committed rat bone marrow SCLC to the SC fate. Therefore, in this study, we explored whether hiPSC-dSNs could mimic rat DRG neurons effects to obtain fate-committed SCs from hBMSC-derived SCLC. The derived cells exhibited bi-/tri-polar morphology of SCs and maintained the expression of the SC markers S100, p75NTR, p0, GFAP, and Sox10, even after withdrawing the glia-inducing factors or hiPSC-dSNs cues. Electronic microscopy and RNA-seq analysis further provided evidence that human BMSC-dSCs were similar to the original human SCs in terms of their function and a variety of characteristics. Furthermore, these cells formed myelin basic protein-positive segments and secreted neurotrophic factors to facilitate the neurite outgrowth of Neuro2A, demonstrating that they were functionally mature. Our results provide a promising approach through which stable and fully developed hBMSC-dSCs can be used for transplantation and myelin sheath regeneration following traumatic nerve injuries. Overall design: To further confirm the schwann cell-lineage identity of hBMSC-dSCs, we performed RNA-seq to compare the gene expression profiles of hBMSCs, human SCs and hBMSC-dSCs.