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Highly efficient and large-scale generation of functional dopamine neurons from human embryonic stem cells

Cited 194 time in Web of Science Cited 204 time in Scopus
Authors
Cho, Myung Soo; Lee, Young-Eun; Kim, Ji Young; Chung, Seungsoo; Cho, Yoon Hee; Kim, Dae-Sung; Kang, Sang-Moon; Lee, Haksup; Kim, Myung-Hwa; Kim, Jeong-Hoon; Leem, Joong Woo; Oh, Sun Kyung; Choi, Young Min; Hwang, Dong-Youn; Chang, Jin Woo; Kim, Dong-Wook
Issue Date
2008-02-29
Publisher
National Academy of Sciences
Citation
Proc Natl Acad Sci U S A. 105(9):3392-3397
Keywords
AnimalsCell Culture Techniques/*methods*Cell DifferentiationCell TransplantationDisease Models, Animal*DopamineEmbryonic Stem Cells/*cytologyHumansMethodsNeurons/*cytology/*transplantationParkinson Disease/therapyRats
Abstract
We developed a method for the efficient generation of functional dopaminergic (DA) neurons from human embryonic stem cells (hESCs) on a large scale. The most unique feature of this method is the generation of homogeneous spherical neural masses (SNMs) from the hESC-derived neural precursors. These SNMs provide several advantages: (i) they can be passaged for a long time without losing their differentiation capability into DA neurons; (ii) they can be coaxed into DA neurons at much higher efficiency than that from previous reports (86% tyrosine hydroxylase-positive neurons/total neurons); (iii) the induction of DA neurons from SNMs only takes 14 days; and (iv) no feeder cells are required during differentiation. These advantages allowed us to obtain a large number of DA neurons within a short time period and minimized potential contamination of unwanted cells or pathogens coming from the feeder layer. The highly efficient differentiation may not only enhance the efficacy of the cell therapy but also reduce the potential tumor formation from the undifferentiated residual hESCs. In line with this effect, we have never observed any tumor formation from the transplanted animals used in our study. When grafted into a parkinsonian rat model, the hESC-derived DA neurons elicited clear behavioral recovery in three behavioral tests. In summary, our study paves the way for the large-scale generation of purer and functional DA neurons for future clinical applications.
ISSN
1091-6490 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18305158

http://www.pnas.org/content/105/9/3392.full.pdf

http://hdl.handle.net/10371/67933
DOI
https://doi.org/10.1073/pnas.0712359105
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College of Medicine/School of Medicine (의과대학/대학원)Obstetrics & Gynecology (산부인과전공)Journal Papers (저널논문_산부인과학전공)
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