Conditions for Tumor-free and Dopamine Neuron-enriched Grafts After Transplanting Human ES Cell-derived Neural Precursor Cells
- Authors
- Ko, Ji-Yun; Lee, Hyun-Seob; Park, Chang-Hwan; Koh, Hyun-Chul; Lee, Yong-Sung; Lee, Sang-Hun
- Issue Date
- Oct-2009
- Publisher
- CELL PRESS
- Citation
- MOLECULAR THERAPY, v.17, no.10, pp.1761 - 1770
- Indexed
- SCIE
SCOPUS
- Journal Title
- MOLECULAR THERAPY
- Volume
- 17
- Number
- 10
- Start Page
- 1761
- End Page
- 1770
- URI
- https://scholarworks.bwise.kr/hanyang/handle/2021.sw.hanyang/176077
- DOI
- 10.1038/mt.2009.148
- ISSN
- 1525-0016
- 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.
- Files in This Item
-
Go to Link
- Appears in
Collections - 서울 의과대학 > 서울 생화학·분자생물학교실 > 1. Journal Articles
- 서울 의과대학 > 서울 약리학교실 > 1. Journal Articles
- 서울 의생명공학전문대학원 > 서울 의생명과학과 > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.