title: Implantable tissue-engineered blood vessels from human induced pluripotent stem cells.
abstract: Derivation of functional vascular smooth muscle cells (VSMCs) from human induced pluripotent stem cells (hiPSCs) to generate tissue-engineered blood vessels (TEBVs) holds great potential in treating patients with vascular diseases. Herein, hiPSCs were differentiated into alpha-smooth muscle actin (α-SMA) and calponin-positive VSMCs, which were seeded onto polymer scaffolds in bioreactors for vascular tissue growth. A functional TEBV with abundant collagenous matrix and sound mechanics resulted, which contained cells largely positive for α-SMA and smooth muscle myosin heavy chain (SM-MHC). Moreover, when hiPSC-derived TEBV segments were implanted into nude rats as abdominal aorta interposition grafts, they remained unruptured and patent with active vascular remodeling, and showed no evidence of teratoma formation during a 2-week proof-of-principle study. Our studies represent the development of the first implantable TEBVs based on hiPSCs, and pave the way for developing autologous or allogeneic grafts for clinical use in patients with vascular disease.
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Anesthesiology, Yale University, New Haven, CT 06519, USA.
authors.forename: Liqiong
authors.initials: L
authors.lastname: Gui
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06520, USA; Department of Surgery, Yale University, New Haven, CT 06520, USA.
authors.forename: Biraja C
authors.initials: BC
authors.lastname: Dash
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jiesi
authors.initials: J
authors.lastname: Luo
authors.affiliation: Department of Surgery, Yale University, New Haven, CT 06520, USA.
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Qin
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Anesthesiology, Yale University, New Haven, CT 06519, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Department of Surgery, Yale University, New Haven, CT 06520, USA.
authors.forename: Kota
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Surgery, Yale University, New Haven, CT 06520, USA.
authors.forename: Takuya
authors.initials: T
authors.lastname: Hashimoto
authors.affiliation: Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06520, USA.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Wu
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Surgery, Yale University, New Haven, CT 06520, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Dardik
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Surgery, Yale University, New Haven, CT 06520, USA.
authors.forename: George
authors.initials: G
authors.lastname: Tellides
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Department of Anesthesiology, Yale University, New Haven, CT 06519, USA; Department of Biomedical Engineering, Yale University, New Haven, CT 06519, USA; Yale Stem Cell Center, New Haven, CT 06520, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Niklason
authors.affiliation: Vascular Biology and Therapeutics Program, Yale University School of Medicine, New Haven, CT 06520, USA; Yale Cardiovascular Research Center, Section of Cardiovascular Medicine, Department of Internal Medicine Yale School of Medicine, New Haven, CT 06520, USA; Yale Stem Cell Center, New Haven, CT 06520, USA; Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA. Electronic address: yibing.qyang@yale.edu.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Qyang
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D011923:Rats, Nude; D023822:Tissue Engineering / Q000379:methods*; D054457:Tissue Scaffolds / Q000737:chemistry
keywords: Human induced pluripotent stem cell; Implantation; Smooth muscle cell; Tissue engineering; Vascular graft