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2015 ; 5
(ä): 11019
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Generation of pure lymphatic endothelial cells from human pluripotent stem cells
and their therapeutic effects on wound repair
#MMPMID26066093
Lee SJ
; Park C
; Lee JY
; Kim S
; Kwon PJ
; Kim W
; Jeon YH
; Lee E
; Yoon YS
Sci Rep
2015[Jun]; 5
(ä): 11019
PMID26066093
show ga
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.