Generation of pure lymphatic endothelial cells from human pluripotent stem cells and their therapeutic effects on wound repair
Identifieur interne : 001D43 ( Main/Exploration ); précédent : 001D42; suivant : 001D44Generation of pure lymphatic endothelial cells from human pluripotent stem cells and their therapeutic effects on wound repair
Auteurs : Shin-Jeong Lee ; Changwon Park [États-Unis] ; Ji Yoon Lee [Corée du Sud] ; Sangsung Kim ; Pil Jae Kwon ; Woansang Kim ; Yong Heui Jeon ; Eugine Lee ; Young-Sup Yoon [Corée du Sud]Source :
- Scientific Reports [ 2045-2322 ] ; 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
Url:
DOI: 10.1038/srep11019
PubMed: 26066093
PubMed Central: 4464258
Affiliations:
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strict</wicri:regionArea></affiliation></author><author><name sortKey="Lee, Ji Yoon" sort="Lee, Ji Yoon" uniqKey="Lee J" first="Ji Yoon" last="Lee">Ji Yoon Lee</name><affiliation><nlm:aff id="a1"><institution>Division of Cardiology, Department of Medicine</institution></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Severance Biomedical Science Institute</institution>, Yonsei University College of Medicine, Seoul,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Sangsung" sort="Kim, Sangsung" uniqKey="Kim S" first="Sangsung" last="Kim">Sangsung Kim</name><affiliation><nlm:aff id="a1"><institution>Division of Cardiology, Department of Medicine</institution></nlm:aff></affiliation></author><author><name sortKey="Kwon, Pil Jae" sort="Kwon, Pil Jae" uniqKey="Kwon P" first="Pil Jae" last="Kwon">Pil Jae 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Department of Medicine</institution></nlm:aff></affiliation></author><author><name sortKey="Park, Changwon" sort="Park, Changwon" uniqKey="Park C" first="Changwon" last="Park">Changwon Park</name><affiliation><nlm:aff id="a1"><institution>Division of Cardiology, Department of Medicine</institution></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="a2"><institution>Department of Pediatrics, Emory University School of Medicine</institution>, Atlanta, GA, 30322,<country>USA</country></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Lee, Ji Yoon" sort="Lee, Ji Yoon" uniqKey="Lee J" first="Ji Yoon" last="Lee">Ji Yoon Lee</name><affiliation><nlm:aff id="a1"><institution>Division of Cardiology, Department of Medicine</institution></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Severance Biomedical Science Institute</institution>, Yonsei University College of Medicine, Seoul,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Kim, Sangsung" sort="Kim, Sangsung" uniqKey="Kim S" first="Sangsung" last="Kim">Sangsung Kim</name><affiliation><nlm:aff id="a1"><institution>Division of Cardiology, Department of Medicine</institution></nlm:aff></affiliation></author><author><name sortKey="Kwon, Pil Jae" sort="Kwon, Pil Jae" uniqKey="Kwon P" first="Pil Jae" last="Kwon">Pil Jae Kwon</name><affiliation><nlm:aff id="a1"><institution>Division of Cardiology, Department of Medicine</institution></nlm:aff></affiliation></author><author><name sortKey="Kim, Woansang" sort="Kim, Woansang" uniqKey="Kim W" first="Woansang" last="Kim">Woansang Kim</name><affiliation><nlm:aff id="a1"><institution>Division of Cardiology, Department of Medicine</institution></nlm:aff></affiliation></author><author><name sortKey="Jeon, Yong Heui" sort="Jeon, Yong Heui" uniqKey="Jeon Y" first="Yong Heui" last="Jeon">Yong Heui Jeon</name><affiliation><nlm:aff id="a1"><institution>Division of Cardiology, Department of Medicine</institution></nlm:aff></affiliation></author><author><name sortKey="Lee, Eugine" sort="Lee, Eugine" uniqKey="Lee E" first="Eugine" last="Lee">Eugine Lee</name><affiliation><nlm:aff id="a1"><institution>Division of Cardiology, Department of Medicine</institution></nlm:aff></affiliation></author><author><name sortKey="Yoon, Young Sup" sort="Yoon, Young Sup" uniqKey="Yoon Y" first="Young-Sup" last="Yoon">Young-Sup Yoon</name><affiliation><nlm:aff id="a1"><institution>Division of Cardiology, Department of Medicine</institution></nlm:aff></affiliation><affiliation wicri:level="1"><nlm:aff id="a3"><institution>Severance Biomedical Science Institute</institution>, Yonsei University College of Medicine, Seoul,<country>Korea</country></nlm:aff><country xml:lang="fr">Corée du Sud</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Scientific Reports</title><idno type="eISSN">2045-2322</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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<sup>+</sup>PODOPLANIN<sup>+</sup>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 <italic>in vivo</italic> 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.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Banerji, S" uniqKey="Banerji S">S. Banerji</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Breiteneder Geleff, S" uniqKey="Breiteneder Geleff S">S. Breiteneder-Geleff</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Francois, M" uniqKey="Francois M">M. Francois</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kaipainen, A" uniqKey="Kaipainen A">A. Kaipainen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wetterwald, A" uniqKey="Wetterwald A">A. Wetterwald</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wigle, J T" uniqKey="Wigle J">J. T. 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Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Baluk, P" uniqKey="Baluk P">P. Baluk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huggenberger, R" uniqKey="Huggenberger R">R. Huggenberger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kataru, R P" uniqKey="Kataru R">R. P. Kataru</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Takahashi, K" uniqKey="Takahashi K">K. Takahashi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Thomson, J A" uniqKey="Thomson J">J. A. Thomson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cho, H J" uniqKey="Cho H">H. J. Cho</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Corée du Sud</li><li>États-Unis</li></country></list><tree><noCountry><name sortKey="Jeon, Yong Heui" sort="Jeon, Yong Heui" uniqKey="Jeon Y" first="Yong Heui" last="Jeon">Yong Heui Jeon</name><name sortKey="Kim, Sangsung" sort="Kim, Sangsung" uniqKey="Kim S" first="Sangsung" last="Kim">Sangsung Kim</name><name sortKey="Kim, Woansang" sort="Kim, Woansang" uniqKey="Kim W" first="Woansang" last="Kim">Woansang Kim</name><name sortKey="Kwon, Pil Jae" sort="Kwon, Pil Jae" uniqKey="Kwon P" first="Pil Jae" last="Kwon">Pil Jae Kwon</name><name sortKey="Lee, Eugine" sort="Lee, Eugine" uniqKey="Lee E" first="Eugine" last="Lee">Eugine Lee</name><name sortKey="Lee, Shin Jeong" sort="Lee, Shin Jeong" uniqKey="Lee S" first="Shin-Jeong" last="Lee">Shin-Jeong Lee</name></noCountry><country name="États-Unis"><noRegion><name sortKey="Park, Changwon" sort="Park, Changwon" uniqKey="Park C" first="Changwon" last="Park">Changwon Park</name></noRegion></country><country name="Corée du Sud"><noRegion><name sortKey="Lee, Ji Yoon" sort="Lee, Ji Yoon" uniqKey="Lee J" first="Ji Yoon" last="Lee">Ji Yoon Lee</name></noRegion><name sortKey="Yoon, Young Sup" sort="Yoon, Young Sup" uniqKey="Yoon Y" first="Young-Sup" last="Yoon">Young-Sup Yoon</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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