title: Induced Pluripotent Stem Cell-Derived Endothelial Cells Overexpressing Interleukin-8 Receptors A/B and/or C-C Chemokine Receptors 2/5 Inhibit Vascular Injury Response.
abstract: Recruitment of neutrophils and monocytes/macrophages to the site of vascular injury is mediated by binding of chemoattractants to interleukin (IL) 8 receptors RA and RB (IL8RA/B) C-C chemokine receptors (CCR) 2 and 5 expressed on neutrophil and monocyte/macrophage membranes. Endothelial cells (ECs) derived from rat-induced pluripotent stem cells (RiPS) were transduced with adenovirus containing cDNA of IL8RA/B and/or CCR2/5. We hypothesized that RiPS-ECs overexpressing IL8RA/B (RiPS-IL8RA/B-ECs), CCR2/5 (RiPS-CCR2/5-ECs), or both receptors (RiPS-IL8RA/B+CCR2/5-ECs) will inhibit inflammatory responses and neointima formation in balloon-injured rat carotid artery. Twelve-week-old male Sprague-Dawley rats underwent balloon injury of the right carotid artery and intravenous infusion of (a) saline vehicle, (b) control RiPS-Null-ECs (ECs transduced with empty virus), (c) RiPS-IL8RA/B-ECs, (d) RiPS-CCR2/5-ECs, or (e) RiPS-IL8RA/B+CCR2/5-ECs. Inflammatory mediator expression and leukocyte infiltration were measured in injured and uninjured arteries at 24 hours postinjury by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. Neointima formation was assessed at 14 days postinjury. RiPS-ECs expressing the IL8RA/B or CCR2/5 homing device targeted the injured arteries and decreased injury-induced inflammatory cytokine expression, neutrophil/macrophage infiltration, and neointima formation. Transfused RiPS-ECs overexpressing IL8RA/B and/or CCR2/5 prevented inflammatory responses and neointima formation after vascular injury. Targeted delivery of iPS-ECs with a homing device to inflammatory mediators in injured arteries provides a novel strategy for the treatment of cardiovascular diseases. Stem Cells Translational Medicine 2017;6:1168-1177.
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Samantha
authors.initials: S
authors.lastname: Giordano
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
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, USA.
authors.forename: Yiu-Fai
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Division of Anatomic Pathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Silvio H
authors.initials: SH
authors.lastname: Litovsky
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.|Section of Cardiology, Birmingham Veterans Affairs Medical Center, Birmingham, Alabama, USA.
authors.forename: Fadi G
authors.initials: FG
authors.lastname: Hage
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Tim M
authors.initials: TM
authors.lastname: Townes
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Chiao-Wang
authors.initials: CW
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Li-Chen
authors.initials: LC
authors.lastname: Wu
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Oparil
authors.affiliation: Vascular Biology and Hypertension Program, Division of Cardiovascular Disease, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Dongqi
authors.initials: D
authors.lastname: Xing
mesh_terms: D000818:Animals; D064987:Cell- and Tissue-Based Therapy; D042783:Endothelial Cells / Q000166:cytology* / Q000378:metabolism*; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054390:Receptors, CCR2 / Q000378:metabolism*; D019713:Receptors, CCR5 / Q000378:metabolism*; D053700:Receptors, Interleukin-8 / Q000378:metabolism*; D057772:Vascular System Injuries / Q000378:metabolism* / Q000628:therapy*
chemical_list: D054390:Receptors, CCR2; D019713:Receptors, CCR5; D053700:Receptors, Interleukin-8
keywords: C-C chemokine receptor 2/5; Interleukin 8 receptor; Targeted cell therapy; Vascular injury; iPS-endothelial cells