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PSA-NCAM-negative neural crest cells emerging during neural induction of pluripotent stem cells cause mesodermal tumors and unwanted grafts

Authors
 Dongjin R. Lee  ;  Jeong-Eun Yoo  ;  Jae Souk Lee  ;  Sanghyun Park  ;  Junwon Lee  ;  Chul-Yong Park  ;  Eunhyun Ji  ;  Han-Soo Kim  ;  Dong-Youn Hwang  ;  Dae-Sung Kim  ;  Dong-Wook Kim 
Citation
 Stem Cell Reports, Vol.4(5) : 821-834, 2015 
Journal Title
 Stem Cell Reports 
ISSN
 2213-6711 
Issue Date
2015
Abstract
Tumorigenic potential of human pluripotent stem cells (hPSCs) is an important issue in clinical applications. Despite many efforts, PSC-derived neural precursor cells (NPCs) have repeatedly induced tumors in animal models even though pluripotent cells were not detected. We found that polysialic acid-neural cell adhesion molecule (PSA-NCAM)(-) cells among the early NPCs caused tumors, whereas PSA-NCAM(+) cells were nontumorigenic. Molecular profiling, global gene analysis, and multilineage differentiation of PSA-NCAM(-) cells confirm that they are multipotent neural crest stem cells (NCSCs) that could differentiate into both ectodermal and mesodermal lineages. Transplantation of PSA-NCAM(-) cells in a gradient manner mixed with PSA-NCAM(+) cells proportionally increased mesodermal tumor formation and unwanted grafts such as PERIPHERIN(+) cells or pigmented cells in the rat brain. Therefore, we suggest that NCSCs are a critical target for tumor prevention in hPSC-derived NPCs, and removal of PSA-NCAM(-) cells eliminates the tumorigenic potential originating from NCSCs after transplantation.
Full Text
http://www.sciencedirect.com/science/article/pii/S2213671115001022
DOI
10.1016/j.stemcr.2015.04.002
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
김동욱(Kim, Dong Wook) ORCID logo https://orcid.org/0000-0002-5025-1532
김한수(Kim, Han Soo)
박상현(Park, Sang Hyun)
박철용(Park, Chul Yong) ORCID logo https://orcid.org/0000-0002-4467-9268
유정은(Yoo, Jeong Eun)
이동진(Lee, Dongjin R.)
이재석(Lee, Jae Souk)
이준원(Lee, Jun Won) ORCID logo https://orcid.org/0000-0003-0543-7132
지은현(Ji, Eun Hyun)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140435
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