Open AccessNoggin Enhances Dopamine Neuron Production from Human Embryonic Stem Cells and Improves Behavioral Outcome After Transplantation into Parkinsonian Rats
Author(s) -
Chiba Shunmei,
Lee Young Mook,
Zhou Wenbo,
Freed Curt R.
Publication year - 2008
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1634/stemcells.2008-0085
Subject(s) - noggin , biology , embryonic stem cell , transplantation , dopamine , stem cell , microbiology and biotechnology , neuron , medicine , endocrinology , neuroscience , bone morphogenetic protein , genetics , gene
Symptoms of Parkinson's disease have been improved by transplantation of fetal dopamine neurons recovered from aborted fetal tissue, but tissue recovery is difficult. Human embryonic stem cells may provide unlimited cells for transplantation if they can be converted to dopamine neurons and survive transplantation into brain. We have found that the bone morphogenic protein antagonist Noggin increased the number of dopamine neurons generated in vitro from human and mouse embryonic stem cells differentiated on mouse PA6 stromal cells. Noggin effects were seen with either early (for mouse, days 0–7, and for human, days 0–9) or continuous treatment. After transplant into cyclosporin‐immunosuppressed rats, human dopamine neurons improved apomorphine circling in direct relation to the number of surviving dopamine neurons, which was fivefold greater after Noggin treatment than with control human embryonic stem cell transplants differentiated only on PA6 cells. We conclude that Noggin promotes dopamine neuron differentiation and survival from human and mouse embryonic stem cells. Disclosure of potential conflicts of interest is found at the end of this article.