title: Targeted delivery of human iPS-ECs overexpressing IL-8 receptors inhibits neointimal and inflammatory responses to vascular injury in the rat.
abstract: Interleukin-8 (IL8) is highly expressed by injured arteries in a variety of diseases and is a chemoattractant for neutrophils which express IL8 receptors IL8RA and RB (IL8RA/B) on their membranes. Neutrophils interact with the damaged endothelium and initiate an inflammatory cascade at the site of injury. We have generated a novel translational targeted cell therapy for acute vascular injury using adenoviral vectors to overexpress IL8RA/B and green fluorescent protein (GFP) on the surface of endothelial cells (ECs) derived from human induced pluripotent stem cells (HiPS-IL8RA/B-ECs). We hypothesize that HiPS-IL8RA/B-ECs transfused intravenously into rats with balloon injury of the carotid artery will target to the injured site and compete with neutrophils, thus inhibiting inflammation and neointima formation. Young adult male Sprague-Dawley rats underwent balloon injury of the right carotid artery and received intravenous transfusion of saline vehicle, 1.5 × 10(6) HiPS-ECs, 1.5 × 10(6) HiPS-Null-ECs, or 1.5 × 10(6) HiPS-IL8RA/B-ECs immediately after endoluminal injury. Tissue distribution of HiPS-IL8RA/B-ECs was analyzed by a novel GFP DNA qPCR method. Cytokine and chemokine expression and leukocyte infiltration were measured in injured and uninjured arteries at 24 h postinjury by ELISA and immunohistochemistry, respectively. Neointimal, medial areas, and reendothelialization were measured 14 days postinjury. HiPS-IL8RA/B-ECs homed to injured arteries, inhibited inflammatory mediator expression and inflammatory cell infiltration, accelerated reendothelialization, and attenuated neointima formation after endoluminal injury while control HiPS-ECs and HiPS-Null-ECs did not. HiPS-IL8RA/B-ECs transfused into rats with endoluminal carotid artery injury target to the injured artery and provide a novel strategy to treat vascular injury.
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Samantha
authors.initials: S
authors.lastname: Giordano
authors.affiliation: Department of Pulmonary, Critical Care, Sleep and Allergy, College of Medicine, University of Illinois at Chicago, Chicago, Illinois;
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Daisy
authors.initials: D
authors.lastname: Xing
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; Division of Cardiology, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama;
authors.forename: Fadi
authors.initials: F
authors.lastname: Hage
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama;
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.affiliation: Houston Methodist Research Institute, Houston, Texas;
authors.forename: John P
authors.initials: JP
authors.lastname: Cooke
authors.affiliation: Division of Cardiovascular Medicine, Stanford University, Stanford, California;
authors.forename: Jieun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Cardiovascular Institute, Stanford University, Stanford, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California; and.
authors.forename: Karina H
authors.initials: KH
authors.lastname: Nakayama
authors.affiliation: Cardiovascular Institute, Stanford University, Stanford, California; Veterans Affairs Palo Alto Health Care System, Palo Alto, California; and Department of Cardiothoracic Surgery, Stanford University, Stanford, California.
authors.forename: Ngan F
authors.initials: NF
authors.lastname: Huang
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; yfchen@uab.edu.
authors.forename: Yiu-Fai
authors.initials: YF
authors.lastname: Chen
mesh_terms: D000818:Animals; D002339:Carotid Arteries / Q000276:immunology / Q000473:pathology*; D020212:Carotid Artery Injuries / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods*; D042783:Endothelial Cells; D004797:Enzyme-Linked Immunosorbent Assay; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation*; D007249:Inflammation; D008297:Male; D058426:Neointima / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D016133:Polymerase Chain Reaction; D051381:Rats; D017207:Rats, Sprague-Dawley; D053700:Receptors, Interleukin-8 / Q000235:genetics / Q000276:immunology*
chemical_list: D053700:Receptors, Interleukin-8; D049452:Green Fluorescent Proteins
keywords: endothelial cells; human induced pluripotent stem cells; inflammation vascular injury; restenosis; targeted cell therapy; vascular injury