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Highly pure and expandable PSA-NCAM-positive neural precursors from human ESC and iPSC-derived neural rosettes

Authors
 Dae-Sung Kim  ;  Dongjin R. Lee  ;  Dong-Wook Kim  ;  Sung-Rae Cho  ;  Taick Sang Nam  ;  Joong Woo Leem  ;  Dong-Youn Hwang  ;  Seungkwon You  ;  Hoon-Chul Kang  ;  Jiho Jang  ;  Bo Young Lim  ;  Sung Jun Jung  ;  Jeong-Eun Yoo  ;  Han-Soo Kim 
Citation
 PLoS One, Vol.7(7) : e39715, 2012 
Journal Title
 PLoS One 
ISSN
 1932-6203 
Issue Date
2012
Abstract
Homogeneous culture of neural precursor cells (NPCs) derived from human pluripotent stem cells (hPSCs) would provide a powerful tool for biomedical applications. However, previous efforts to expand mechanically dissected neural rosettes for cultivation of NPCs remain concerns regarding non-neural cell contamination. In addition, several attempts to purify NPCs using cell surface markers have not demonstrated the expansion capability of the sorted cells. In the present study, we show that polysialic acid-neural cell adhesion molecule (PSA-NCAM) is detected in neural rosette cells derived from hPSCs, and employ PSA-NCAM as a marker for purifying expandable primitive NPCs from the neural rosettes. PSA-NCAM-positive NPCs (termed hNPC(PSA-NCAM+)) were isolated from the heterogeneous cell population of mechanically harvested neural rosettes using magnetic-based cell sorting. The hNPC(PSA-NCAM+) extensively expressed neural markers such as Sox1, Sox2, Nestin, and Musashi-1 (80∼98% of the total cells) and were propagated for multiple passages while retaining their primitive characteristics in our culture condition. Interestingly, PSA-NCAM-negative cells largely exhibited characteristics of neural crest cells. The hNPC(PSA-NCAM+) showed multipotency and responsiveness to instructive cues towards region-specific neuronal subtypes in vitro. When transplanted into the rat striatum, hNPC(PSA-NCAM+) differentiated into neurons, astrocytes, and oligodendrocytes without particular signs of tumorigenesis. Furthermore, Ki67-positive proliferating cells and non-neural lineage cells were rarely detected in the grafts of hNPC(PSA-NCAM+) compared to those of neural rosette cells. Our results suggest that PSA-NCAM-mediated cell isolation provides a highly expandable population of pure primitive NPCs from hPSCs that will lend themselves as a promising strategy for drug screening and cell therapy for neurodegenerative disorders.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91711
DOI
10.1371/journal.pone.0039715
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Physiology (생리학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실)
Yonsei Authors
강훈철(Kang, Hoon Chul) ; 김대성(Kim, Dae Sung) ; 김동욱(Kim, Dong Wook) ; 김한수(Kim, Han Soo) ; 남택상(Nam, Taick Sang) ; 임중우(Leem, Joong Woo) ; 장지호(Jang, Ji Ho) ; 조성래(Cho, Sung Rae)
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