Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington's disease

Mol Cell Neurosci. 2008 Mar;37(3):454-70. doi: 10.1016/j.mcn.2007.11.001. Epub 2007 Nov 12.

Abstract

Neural and mesenchymal stem cells have been proposed as alternative sources of cells for transplantation into the brain in neurodegenerative disorders. However, the endogenous factors controlling their engraftment within the injured parenchyma remain ill-defined. Here, we demonstrate significant engraftment of undifferentiated exogenous mesenchymal or neural stem cells throughout the lesioned area in a rat model for Huntington's disease, as late as 8 weeks post-transplantation. We show that stem cell factor (SCF), strongly up-regulated within host cells in the damaged striatum, is able to activate the SCF receptor c-kit and its signaling pathway and to promote the migration and proliferation of mesenchymal and neural stem cells in vitro. Furthermore, c-kit receptor blockade alters neural stem cell distribution within the lesioned striatum. Host SCF expression is observed in atypical cells expressing glial fibrillary acidic protein and doublecortin in the lesioned striatum and in migrating doublecortin-positive progenitors. Taken together, these data demonstrate that SCF produced in situ in the lesioned striatum is an important factor in promoting the engraftment of stem cells within the lesioned brain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cell Count / methods
  • Cell Differentiation / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Proliferation / radiation effects
  • Cells, Cultured
  • Corpus Striatum / pathology
  • Disease Models, Animal
  • Embryo, Mammalian
  • Huntington Disease / etiology
  • Huntington Disease / pathology
  • Huntington Disease / surgery*
  • Male
  • Nerve Tissue Proteins / metabolism
  • Neurons / drug effects
  • Neurons / physiology*
  • Organic Chemicals / metabolism
  • Proto-Oncogene Proteins c-kit / metabolism
  • Rats
  • Rats, Wistar
  • Stem Cell Factor / pharmacology*
  • Stem Cell Transplantation / methods*
  • Stem Cells / classification
  • Stem Cells / drug effects*
  • Stem Cells / physiology*
  • Time Factors

Substances

  • Nerve Tissue Proteins
  • Organic Chemicals
  • PKH 26
  • Stem Cell Factor
  • Proto-Oncogene Proteins c-kit