Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the bone morphogenic protein antagonist noggin

Stem Cells. 2007 Feb;25(2):411-8. doi: 10.1634/stemcells.2006-0380. Epub 2006 Oct 12.

Abstract

It is currently not known whether dopamine (DA) neurons derived from human embryonic stem cells (hESCs) can survive in vivo and alleviate symptoms in models of Parkinson disease (PD). Here, we report the use of Noggin (a bone morphogenic protein antagonist) to induce neuroectodermal cell development and increase the yield of DA neurons from hESCs. A combination of stromal-derived inducing activity and Noggin markedly enhanced the generation of neuroepithelial progenitors that could give rise to DA neurons. In addition, Noggin diminished the occurrence of a fibroblast-like Nestin-positive precursor population that differentiated into myocytes. After transplantation of differentiated hESCs to a rodent model of PD, some grafts contained human midbrain-like DA neurons. This protocol demonstrates hESC derivation and survival of human DA neurons appropriate for cell therapy in PD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Bone Morphogenetic Proteins / antagonists & inhibitors*
  • Carrier Proteins / pharmacology*
  • Cells, Cultured
  • Dopamine / metabolism*
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / drug effects
  • Embryonic Stem Cells / transplantation
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Mesencephalon / cytology*
  • Mesencephalon / drug effects
  • Neuroepithelial Cells / cytology*
  • Neuroepithelial Cells / drug effects
  • Neurons / cytology*
  • Neurons / drug effects
  • Phenotype
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation

Substances

  • Biomarkers
  • Bone Morphogenetic Proteins
  • Carrier Proteins
  • RNA, Messenger
  • noggin protein
  • Dopamine