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

 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 
 STEM CELL REPORTS, Vol.4(5) : 821-834, 2015 
Journal Title
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Animals ; Cell Differentiation ; Cell Lineage ; Cells, Cultured ; Ectoderm/cytology ; Ectoderm/metabolism ; Human Embryonic Stem Cells/cytology ; Humans ; Immunohistochemistry ; Male ; Mesoderm/cytology ; Mesoderm/metabolism ; Neoplasms/etiology ; Neoplasms/metabolism ; Neural Cell Adhesion Molecule L1/genetics ; Neural Cell Adhesion Molecule L1/metabolism* ; Neural Crest/cytology ; Neural Crest/metabolism* ; Neural Crest/transplantation ; Peripherins/metabolism ; Pluripotent Stem Cells/cytology* ; Pluripotent Stem Cells/metabolism ; Rats ; Rats, Sprague-Dawley ; Sialic Acids/genetics ; Sialic Acids/metabolism* ; Transcriptome
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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Ophthalmology (안과학교실) > 1. Journal Papers
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
Yonsei Authors
Kim, Dong Wook(김동욱) ORCID logo https://orcid.org/0000-0002-5025-1532
Kim, Han Soo(김한수)
Park, Sang Hyun(박상현)
Park, Chul Yong(박철용) ORCID logo https://orcid.org/0000-0002-4467-9268
Yoo, Jeong Eun(유정은)
Lee, Dongjin R.(이동진)
Lee, Jae Souk(이재석)
Lee, Jun Won(이준원) ORCID logo https://orcid.org/0000-0003-0543-7132
Ji, Eun Hyun(지은현)
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