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

 Shin-Jeong Lee  ;  Changwon Park  ;  Ji Yoon Lee  ;  Sangsung Kim  ;  Pil Jae Kwon  ;  Woansang Kim  ;  Yong Heui Jeon  ;  Eugine Lee  ;  Young-sup Yoon 
 SCIENTIFIC REPORTS, Vol.5 : 11019, 2015 
Journal Title
Issue Date
Animals ; Cell Differentiation* ; Cell- and Tissue-Based Therapy* ; Endothelial Cells/cytology ; Endothelial Cells/metabolism* ; Endothelial Cells/transplantation ; Epidermal Growth Factor/pharmacology ; Heterografts ; Humans ; Lymphangiogenesis* ; Mice ; Mice, Nude ; Pluripotent Stem Cells ; Vascular Endothelial Growth Factor A/pharmacology ; Vascular Endothelial Growth Factor C/pharmacology ; Wound Healing*
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.
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1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
Yonsei Authors
Yoon, Young Sup(윤영섭)
Lee, Ji Yoon(이지윤)
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