Spotlight on Research

Roy N. Alcalay, M.D.
"Why do some people who carry genetic mutations associated with Parkinson’s disease (PD) never develop PD while others do?" asks Roy N. Alcalay, M.D., a postdoctoral fellow at the Center for Parkinson’s Disease and Other Movement Disorders...
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Conditions for Tumor-free and Dopamine Neuron-enriched Grafts After Transplanting Human ES Cell-derived Neural Precursor Cells.
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Mol Ther 2009 Jul;
Authors: Ji-Yun Ko, Hyun-Seob Lee, Chang-Hwan Park, Hyun-Chul Koh, Yong-Sung Lee, Sang-Hun Lee
[1] Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul, Korea [2] Medical Research Center, Hanyang University, Seoul, Korea.
We have previously demonstrated derivation of neural precursor (NP) cells of a midbrain-type from human embryonic stem (hES) cells to yield an enriched population of dopamine (DA) neurons. These hES-derived NPs can be expanded in vitro through multiple passages without altering their DA neurogenic potential. Here, we studied two aspects of these hES-NP cells that are critical issues in cell therapeutic approaches for Parkinson's disease (PD): cell survival and tumorigenic potential. Neuroepithelial rosettes, a potentially tumorigenic structure, disappeared during hES-NP cell expansion in vitro. Although a minor population of cells positive for Oct3/4, a marker specific for undifferentiated hES cells, persisted in culture during hES-NP cell expansion, they could be completely eliminated by subculturing hES-NPs under differentiation-inducing conditions. Consistently, no tumors/teratomas are formed in rats grafted with multipassaged hES-NPs. However, extensively expanded hES-NP cells easily underwent cell death during differentiation in vitro and after transplantation in vivo. Transgenic expression of Bcl-XL and sonic hedgehog (SHH) completely overcame the cell survival problems without increasing tumor formation. These findings indicate that hES-NP cell expansion in conjunction with Bcl-XL+SHH transgene expression may provide a renewable and safe source of DA neurons for transplantation in PD.Molecular Therapy (2009); doi:10.1038/mt.2009.148.
PMID: 19603007 [PubMed - as supplied by publisher]










