title: Enhanced yield of neuroepithelial precursors and midbrain-like dopaminergic neurons from human embryonic stem cells using the bone morphogenic protein antagonist noggin.
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.
authors.affiliation: Center for Neuroregeneration Research, Udall Parkinson's Disease Center of Excellence, McLean Hospital, Harvard Medical School, Belmont, Massachusetts 02478, USA. kai.sonntag@mclean.harvard.edu
authors.forename: Kai-Christian
authors.initials: KC
authors.lastname: Sonntag
authors.forename: Jan
authors.initials: J
authors.lastname: Pruszak
authors.forename: Takahito
authors.initials: T
authors.lastname: Yoshizaki
authors.forename: Joris
authors.initials: J
authors.lastname: van Arensbergen
authors.forename: Rosario
authors.initials: R
authors.lastname: Sanchez-Pernaute
authors.forename: Ole
authors.initials: O
authors.lastname: Isacson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008636:Mesencephalon / Q000166:cytology* / Q000187:drug effects; D046569:Neuroepithelial Cells / Q000166:cytology* / Q000187:drug effects; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D033581:Stem Cell Transplantation; D000099176:Noggin Protein
chemical_list: D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D004298:Dopamine; D012333:RNA, Messenger; D000099176:Noggin Protein