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

Stem Cell Reports. 2017 Oct 10;9(4):1097-1108. doi: 10.1016/j.stemcr.2017.08.004. Epub 2017 Sep 7.

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.

Keywords: Schwann cell; bone marrow stromal cell; differentiation; fate commitment; myelination.

MeSH terms

  • Axons / metabolism
  • Biomarkers
  • Cell Differentiation*
  • Cells, Cultured
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Gene Expression Profiling
  • Humans
  • Immunophenotyping
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism
  • Myelin Sheath / genetics
  • Myelin Sheath / metabolism
  • Nerve Growth Factors / metabolism
  • Neural Stem Cells / cytology
  • Neural Stem Cells / metabolism
  • Neurites / metabolism
  • Neurogenesis
  • Neurons / cytology
  • Neurons / metabolism
  • Phenotype
  • Schwann Cells / cytology*
  • Schwann Cells / metabolism

Substances

  • Biomarkers
  • Nerve Growth Factors