Extracellular vesicles produced by human-induced pluripotent stem cell-derived endothelial cells can prevent arterial stenosis in mice via autophagy regulation

• DOI: 10.3389/fcvm.2022.922790
• Publication Date: 2022-10-17T04:56:06Z
• Authors: Yecheng He; Quanfu Li; Feng Feng; Rupan Gao; Huadong Li; Yuxin Chu; Shaobo Li; Yin Wang; Ruoying Mao; Zhongzhong Ji; Yutao Hua; Jun Shen; Ziao Wang; Meng Zhao; Qing Yao
• Keywords: Intimal hyperplasia

Intravascular transplantation of human-induced pluripotent stem cells (hiPSCs) demonstrated a significant therapeutic effect in the treatment restenosis by paracrine function extracellular vesicles (EVs). However, risk tumorigenicity and poor cell survival limits its clinical applications. In this study, we for first time applied highly efficient robust three-dimensional (3D) protocol hiPSC differentiation into endothelial (ECs) with subsequent isolation EVs from derived hiPSC-EC (ECs differentiated hiPSCs), validated their intimal hyperplasia (IH) models. We found that intravenously (iv) injected could accumulate on carotid artery endothelium significantly alleviate thickening induced ligation. To elucidate mechanism protection, performed miRNA expression profiling out among most conserved miRNAs, miR-126 was abundant hiPSC-EC-produced (hiPSC-EC-EV). MiR-126 depletion hiPSC-EC-EV can hinder protective human umbilical vein (HUVECs) an inflammatory process. A variety functional vitro studies revealed able to prevent apoptosis after stimulation, as well promote EC migration tube formation through autophagy upregulation. The latter supported vivo demonstrating upregulate mouse ECs, thereby preventing IH modulating vascular homeostasis via remodeling intima. Our findings suggest regulatory arterial regulation, provide potential strategy disease.