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

by: Kai-Christian C Sonntag, Jan Pruszak, Takahito Yoshizaki, Joris van Arensbergen, Rosario Sanchez-Pernaute, Ole Isacson
Stem Cells (12 October 2006)


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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.


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