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

Kai Christian Sonntag, Jan Pruszak, Takahito Yoshizaki, Joris Van Arensbergen, Rosario Sanchez-Pernaute, Ole Isacson

Research output: Contribution to journalArticle

205 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)411-418
Number of pages8
JournalStem Cells
Volume25
Issue number2
DOIs
Publication statusPublished - 2007 Feb 1
Externally publishedYes

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Keywords

  • Differentiation
  • Dopamine
  • Human embryonic stem cells
  • Noggin
  • Parkinson's disease 6-hydroxydopamine-lesioned rats

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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