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First published online October 12, 2006
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2006-0380v1
25/2/411    most recent
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Submitted on June 22, 2006
Accepted on October 5, 2006

Embryonic Stem Cells

Enhanced Yield of Neuroepithelial Precursors and Midbrain-Like Dopaminergic Neurons from Human Embryonic Stem Cells Using the BMP Antagonist Noggin

Kai-Christian Sonntag 1*, Jan Pruszak 1, Takahito Yoshizaki 1, Joris van Arensbergen 1, Rosario Sanchez-Pernaute 1, Ole Isacson 1

1 Center for Neuroregeneration Research, Udall Parkinson's Disease Center of Excellence, McLean Hospital, Harvard Medical School, Belmont, Massachusetts

* To whom correspondence should be addressed. E-mail: kai.sonntag{at}mclean.harvard.edu.


  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's 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 (SDIA) 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 PD, some grafts contained human midbrain-like DA neurons. This protocol demonstrates hESC derivation and survival of hDA neurons appropriate for cell therapy in PD.

Key Words. human embryonic stem cells, dopamine, differentiation, noggin, Parkinson's disease, 6-OHDA lesioned rats




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