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

Authors

  • Kai-Christian Sonntag M.D., Ph.D.,

    Corresponding author
    1. Center for Neuroregeneration Research, Udall Parkinson's Disease Center of Excellence, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA
    • Harvard Medical School, Center for Neuroregeneration Research, MRC 126, McLean Hospital, 115 Mill Street, Belmont, Massachusetts 02478, USA. Telephone: 617-855-3138; Fax: 617-855-3284
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  • Jan Pruszak,

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

    1. Center for Neuroregeneration Research, Udall Parkinson's Disease Center of Excellence, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA
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  • Joris van Arensbergen,

    1. Center for Neuroregeneration Research, Udall Parkinson's Disease Center of Excellence, McLean Hospital, Harvard Medical School, Belmont, Massachusetts, USA
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  • Rosario Sanchez-Pernaute,

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

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

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