Bone marrow-derived Schwann cells achieve fate commitment--a prerequisite for remyelination therapy

Exp Neurol. 2010 Aug;224(2):448-58. doi: 10.1016/j.expneurol.2010.05.005. Epub 2010 May 17.

Abstract

Schwann cell transplantation improves post-traumatic nerve regeneration in both PNS and CNS but sufficient numbers of immunocompatible cells are required for clinical application. Currently, Schwann cell-like cells derived from the bone marrow lack fate commitment and revert to a fibroblast-like phenotype upon withdrawal of differentiation-inducing factors. In recapitulation of embryonic events leading to Schwann cell maturation, we hypothesize that the Schwann cell-like cells acquire the switch to fate commitment through contact-dependent cues from incipient neurons of the developing dorsal root ganglia. To address this, Schwann cell-like cells derived from adult rat bone marrow were cocultured with neurons purified from embryonic dorsal root ganglia. A cell-intrinsic switch to the Schwann cell fate was achieved consistently and the cell progeny maintained expression of the markers S100 beta, p75(NTR) , GFAP, P0 and Sox 10 even without exogenous differentiation-inducing factors or neurons. In vitro formation of MBP-positive segments under myelinating conditions by the cell progeny was comparable to that by sciatic nerve-derived Schwann cells. Controls in which Schwann cell-like cells were barred from direct contact with neurons in coculture reverted to SMA/CD90-expressing myofibroblasts. We demonstrate therefore for the first time fate commitment among bone marrow-derived Schwann cells. The therapeutic potential of these cells may be tested in future transplantation studies. (206 words).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology*
  • Cell Differentiation
  • Cell Lineage
  • Coculture Techniques
  • Colforsin / pharmacology
  • Culture Media
  • Embryo, Mammalian
  • Embryonic Stem Cells / cytology
  • Ganglia, Spinal / cytology
  • Laminin / metabolism
  • Myelin Basic Protein / metabolism
  • Myelin Sheath / metabolism*
  • Neuregulin-1 / pharmacology
  • Neurons / cytology
  • Platelet-Derived Growth Factor / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Schwann Cells / cytology*

Substances

  • Culture Media
  • Laminin
  • Myelin Basic Protein
  • Neuregulin-1
  • Platelet-Derived Growth Factor
  • Colforsin