Region-specific generation of cholinergic neurons from fetal human neural stem cells grafted in adult rat

Nat Neurosci. 2002 Dec;5(12):1271-8. doi: 10.1038/nn974.

Abstract

Pluripotent or multipotent stem cells isolated from human embryos or adult central nervous system (CNS) may provide new neurons to ameliorate neural disorders. A major obstacle, however, is that the majority of such cells do not differentiate into neurons when grafted into non-neurogenic areas of the adult CNS. Here we report a new in vitro priming procedure that generates a nearly pure population of neurons from fetal human neural stem cells (hNSCs) transplanted into adult rat CNS. Furthermore, the grafted cells differentiated by acquiring a cholinergic phenotype in a region-specific manner. This technology may advance stem cell-based therapy to replace lost neurons in neural injury or neurodegenerative disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylcholine / metabolism
  • Animals
  • Brain Tissue Transplantation / methods*
  • Cell Culture Techniques / methods*
  • Cells, Cultured
  • Choline O-Acetyltransferase / metabolism
  • Fetus
  • Graft Survival / drug effects
  • Graft Survival / physiology*
  • Heparin / pharmacology
  • Humans
  • Immunohistochemistry
  • Laminin / pharmacology
  • Male
  • Nerve Growth Factors / pharmacology
  • Neurodegenerative Diseases / therapy*
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Phenotype
  • Rats
  • Stem Cell Transplantation / methods*
  • Stem Cells / cytology*
  • Stem Cells / drug effects
  • Stem Cells / metabolism

Substances

  • Laminin
  • Nerve Growth Factors
  • Heparin
  • Choline O-Acetyltransferase
  • Acetylcholine