Derivation of stable Schwann cells from human bone marrow stromal cells

Abstract

Schwann cell transplantation improves post-traumatic nerve regeneration in both peripheral nervous system and central nervous system but sufficient numbers of immunocompatible cells are required for clinical application. Protocols utilizing multiple trophic and glial growth factors have been established to induce glial-like differentiation of bone marrow stromal cells (BMSCs). However, the reported transition of BMSCs to Schwann cell-like cells was reversible, suggesting against a complete differentiation process. In recapitulation of embryonic events leading to Schwann cell determination, commitment of Schwann cell-like cells into mature Schwann cells can be achieved when they receive necessary signals from neurons of developing dorsal root ganglia. In this study, we mimic the course of Schwann cell development and established a new protocol to fulfill a cell-intrinsic switch of human BMSCs to a Schwann cell fate. As shown by our results, derivatives of human BMSCs underwent the commitment to mature Schwann cells even when all exogenous differentiation-inducing cues are not presented in cultures. First, the derived cells acquired a Schwann cell phenotype indicated by bipolar morphology and expression of Schwann cell markers. Second, these cells maintained myelination capacities, shown by forming basic myelin protein-positive segments along axons of sensory neurons. Third, the gene expression profiles of the derived cells and human Schwann cell line are similar, demonstrated by a high correlation of the two populations. Our success with stable derivation of Schwann cells from human BMSCs offer a viable source of Schwann cells for autologous cell therapy in clinical applications.