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Generation of pure lymphatic endothelial cells from human pluripotent stem cells and their therapeutic effects on wound repair

Authors
 Shin-Jeong Lee ; Changwon Park ; Young-sup Yoon ; Eugine Lee ; Yong Heui Jeon ; Woansang Kim ; Pil Jae Kwon ; Sangsung Kim ; Ji Yoon Lee 
Citation
 Scientific Reports, Vol.5(null) : 11019, 2015 
Journal Title
 Scientific Reports 
ISSN
 2045-2322 
Issue Date
2015
Abstract
Human pluripotent stem cells (hPSCs) have emerged as an important source for cell therapy. However, to date, no studies demonstrated generation of purified hPSC-derived lymphatic endothelial cells (LECs) and tested their therapeutic potential in disease models. Here we sought to differentiate hPSCs into the LEC lineage, purify them with LEC markers, and evaluate their therapeutic effects. We found that an OP9-assisted culture system reinforced by addition of VEGF-A, VEGF-C, and EGF most efficiently generated LECs, which were then isolated via FACS-sorting with LYVE-1 and PODOPLANIN. These hPSC-derived LYVE-1(+)PODOPLANIN(+)cells showed a pure committed LEC phenotype, formed new lymphatic vessels, and expressed lymphangiogenic factors at high levels. These hPSC-derived LECs enhanced wound healing through lymphangiogenesis and lymphvasculogenesis. Here we report, for the first time, that LECs can be selectively isolated from differentiating hPSCs, and that these cells are potent for lymphatic vessel formation in vivo and wound healing. This system and the purified hPSC-derived LECs can serve as a new platform for studying LEC development as well as for cell therapy.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/140550
DOI
10.1038/srep11019
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Life Science
Yonsei Authors
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