title: Generation of pure lymphatic endothelial cells from human pluripotent stem cells and their therapeutic effects on wound repair.
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.
authors.affiliation: Division of Cardiology, Department of Medicine.
authors.forename: Shin-Jeong
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: 1] Division of Cardiology, Department of Medicine [2] Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, 30322, USA.
authors.forename: Changwon
authors.initials: C
authors.lastname: Park
authors.affiliation: 1] Division of Cardiology, Department of Medicine [2] Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Ji Yoon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Division of Cardiology, Department of Medicine.
authors.forename: Sangsung
authors.initials: S
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Medicine.
authors.forename: Pil Jae
authors.initials: PJ
authors.lastname: Kwon
authors.affiliation: Division of Cardiology, Department of Medicine.
authors.forename: Woansang
authors.initials: W
authors.lastname: Kim
authors.affiliation: Division of Cardiology, Department of Medicine.
authors.forename: Yong Heui
authors.initials: YH
authors.lastname: Jeon
authors.affiliation: Division of Cardiology, Department of Medicine.
authors.forename: Eugine
authors.initials: E
authors.lastname: Lee
authors.affiliation: 1] Division of Cardiology, Department of Medicine [2] Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young-sup
authors.initials: YS
authors.lastname: Yoon
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D064987:Cell- and Tissue-Based Therapy; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism* / Q000637:transplantation; D004815:Epidermal Growth Factor / Q000494:pharmacology; D064593:Heterografts; D006801:Humans; D042583:Lymphangiogenesis; D051379:Mice; D008819:Mice, Nude; D039904:Pluripotent Stem Cells; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D042582:Vascular Endothelial Growth Factor C / Q000494:pharmacology; D014945:Wound Healing
chemical_list: C467484:VEGFA protein, human; C467486:VEGFC protein, human; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; D004815:Epidermal Growth Factor