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- Title
Conditions for Tumor-free and Dopamine Neuron–enriched Grafts After Transplanting Human ES Cell–derived Neural Precursor Cells.
- Authors
Ji-Yun Ko; Hyun-Seob Lee; Chang-Hwan Park; Hyun-Chul Koh; Yong-Sung Lee; Sang-Hun Lee
- Abstract
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.
- Publication
Molecular Therapy, 2009, Vol 17, Issue 10, p1761
- ISSN
1525-0016
- Publication type
Academic Journal
- DOI
10.1038/mt.2009.148