Targeted delivery of human iPS-ECs overexpressing IL-8 receptors inhibits neointimal and inflammatory responses to vascular injury in the rat

American Journal of Physiology. Heart and Circulatory Physiology
Samantha GiordanoYiu-Fai Chen

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 i...Continue Reading

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Citations

Jul 7, 2018·Current Protocols in Human Genetics·Mingxia Gu
Oct 14, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Yang LinMervin C Yoder
Apr 12, 2020·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·Meng LuSifeng Chen
Sep 2, 2017·American Journal of Respiratory Cell and Molecular Biology·Andrew J BryantEdward W Scott
Jul 22, 2018·Cellular and Molecular Neurobiology·Lei YeHongwei Cheng
Dec 12, 2019·Frontiers in Bioengineering and Biotechnology·Aneetta E KuriakoseKytai T Nguyen

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