Yiu-Fai Chen
University of Alabama at Birmingham School of Medicine
Title: Using Induced Pluripotent Stem Cells (iPSCs) Derived Endothelial Cells (ECs) to Repair Cardiovascular Injury
Biography
Biography: Yiu-Fai Chen
Abstract
Interleukin-8 receptors A/B (IL8RA/B) are homing device for neutrophils to target injured tissues. We developed an innovative targeted cell therapy using ECs that overexpress IL8RA/B to repair the cardiovascular injury. We transduced rat aortic ECs (RAECs), induced-pluripotent ECs (rat-iPS-ECs), or porcine coronary artery ECs (PCAECs) with adenoviruses carrying IL8RA/B genes. We hypothesize that healthy IL8RA/B-ECs can target injured arteries, thus inhibiting infiltration of neutrophils/macrophages and inflammatory responses, and accelerating re-endothelialization and suppressing the injury-induced neointima formation. In rat model, young male SD rats received balloon injury of the carotid artery and were immediately i.v.transfused with 1) vehicle, 2) 1.5x106 control RAECs or rat-iPS-ECs, or 3) 1.5x106 IL8RA/B-RAECs or rat-iPS-IL8RA/B-ECs. One group of rats were sacrificed 24 hr post injury to measure infiltration of neutrophils/macrophages and pro-inflammatory cytokines expression. Another group was sacrificed 2 wks post injury to measure neointima formation. In pig model, young Yorkshire pigs received stent implantation in the LAD and circumflex coronary arteries and were immediately i.v. transfused with 15x106 IL8RA/B-PCAECs or vehicle. Pigs were sacrificed 4 wks after stenting to measure restenosis. Rats transfused with IL8RA/B-RAECs or rat-iPS-IL8RA/B-ECs had significantly decreased neutrophils/macrophages infiltration, inflammatory cytokines expression, and neointima formation in injured arteries. Pigs transduced with IL8RA/B-PCAECs had reduced injury-induced arterial restenosis. Results indicate that transfused adult ECs or iPS-ECs with overexpression of IL8RA/B mimic the behavior of neutrophils that target to injured vessels, preventing inflammation and restenosis. Targeted delivery of ECs to arteries with endoluminal injury provides a novel strategy for the treatment of cardiovascular diseases.