title: Differentiation of human pluripotent stem cells to cells similar to cord-blood endothelial colony-forming cells.
abstract: The ability to differentiate human pluripotent stem cells into endothelial cells with properties of cord-blood endothelial colony-forming cells (CB-ECFCs) may enable the derivation of clinically relevant numbers of highly proliferative blood vessel-forming cells to restore endothelial function in patients with vascular disease. We describe a protocol to convert human induced pluripotent stem cells (hiPSCs) or embryonic stem cells (hESCs) into cells similar to CB-ECFCs at an efficiency of >10(8) ECFCs produced from each starting pluripotent stem cell. The CB-ECFC-like cells display a stable endothelial phenotype with high clonal proliferative potential and the capacity to form human vessels in mice and to repair the ischemic mouse retina and limb, and they lack teratoma formation potential. We identify Neuropilin-1 (NRP-1)-mediated activation of KDR signaling through VEGF165 as a critical mechanism for the emergence and maintenance of CB-ECFC-like cells.
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Nutan
authors.initials: N
authors.lastname: Prasain
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Man Ryul
authors.initials: MR
authors.lastname: Lee
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Sasidhar
authors.initials: S
authors.lastname: Vemula
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Jonathan Luke
authors.initials: JL
authors.lastname: Meador
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Momoko
authors.initials: M
authors.lastname: Yoshimoto
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ferkowicz
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Alexa
authors.initials: A
authors.lastname: Fett
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Manav
authors.initials: M
authors.lastname: Gupta
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Brian M
authors.initials: BM
authors.lastname: Rapp
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Saadatzadeh
authors.affiliation: Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Ginsberg
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.affiliation: Department of Medicine, the University of Chicago, Chicago, Illinois, USA.
authors.forename: Younghee
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, USA.
authors.forename: Sherry L
authors.initials: SL
authors.lastname: Voytik-Harbin
authors.affiliation: Kon Kuk University School of Medicine, Seoul, South Korea.
authors.forename: Hyung Min
authors.initials: HM
authors.lastname: Chung
authors.affiliation: Stem Cell Research Laboratory, CHA University, Seoul, South Korea.
authors.forename: Ki Sung
authors.initials: KS
authors.lastname: Hong
authors.affiliation: Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Reid
authors.affiliation: Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Christina L
authors.initials: CL
authors.lastname: O'Neill
authors.affiliation: Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Reinhold J
authors.initials: RJ
authors.lastname: Medina
authors.affiliation: Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Stitt
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murphy
authors.affiliation: Howard Hughes Medical Institute, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Shahin
authors.initials: S
authors.lastname: Rafii
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
authors.affiliation: Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Mervin C
authors.initials: MC
authors.lastname: Yoder
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology*; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D051379:Mice; D039942:Neuropilin-1 / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology*; D013234:Stem Cells / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1