Endothelial Progenitor Cell‐Derived Extracellular Vesicles: A Novel Candidate for Regenerative Medicine and Disease Treatment

Abstract

Extracellular vesicles (EVs) are a heterogeneous group of membranous structures, which can be secreted by most cell types. As a product of paracrine secretion, EVs are considered to be a regulatory mediator for intercellular communication. There are many bioactive cargos in EVs, such as proteins, lipids, and nucleic acids. As the precursor cell of vascular endothelial cells (ECs), endothelial progenitor cells (EPCs) are first discovered in peripheral blood. With the development of studies about the functions of EPCs, an increasing number of researchers focus on EPC‐derived EVs (EPC‐EVs). EPC‐EVs exert key functions for promoting angiogenesis in regenerative medicine and show significant therapeutic effects on a variety of diseases such as circulatory diseases, kidney diseases, diabetes, bone diseases, and tissue/organ damages. This article reviews the current knowledge on the role of EPC‐EVs in regenerative medicine and disease treatment, discussing the main challenges and future directions in this field.

Endothelial progenitor cells promote osteogenic differentiation in co-cultured with mesenchymal stem cells via the MAPK-dependent pathway

“…This observed effect may be exerted through exosomes or a variety of paracrine mechanisms [ 59 , 60 ]. It was proved that EPCs create local nutritional support environments by producing microvesicles, exosomes, and growth factors which promote cell proliferation and cell biological motility maintenance [ 61 – 63 ]. It was reported that EPCs derived exosomes transplantation significantly accelerate bone regeneration in rats [ 37 ].…”

Advances in Exosomes Derived from Different Cell Sources and Cardiovascular Diseases

“…These challenges need to be addressed before exosomes can proceed to clinical application. [49] miR-10b-5p Ameliorate cardiac fibroblast activation Preclinical evidences (in vitro) [89] miR-146a-5p and miR-146b-5p Inhibit the migration and angiogenesis Preclinical evidences (in vitro) [88] Macrophages and leukocyte NA Promote vascular smooth muscle cells migration and adhesion, which may be mediated by the integration of extracellular vesicles into vascular smooth muscle cells and the subsequent downstream activation of ERK and Akt Preclinical evidences (in vitro) [51] Biomarkers of atherosclerosis Clinical evidences [50] Cardiac stromal cells miR-21-5p…”

“…The cardiac precursor cell-secreted exosomes rich in PAPP-A had a cardioprotection profile through releasing IGF-1 via proteolytic cleavage of IGFBP-4, resulting in IGF-1R activation and intracellular Akt and ERK1/2 phosphorylation [87]. It was found that exosomes secreted by endothelial progenitor cells derived from patients with coronary atherosclerotic heart disease could inhibit the migration and angiogenesis through expressing more miR-146a-5p and miR-146b-5p [88]. Another study indicated that normoxia endothelial progenitor cell-derived exosomes rich in miR-10b-5p could significantly ameliorate cardiac fibroblast activation in vitro [89].…”

Endothelial progenitor cells promote osteogenic differentiation in co-cultured with mesenchymal stem cells via the MAPK-dependent pathway

“…[59,60]. It was proved that EPCs create local nutritional support environments by producing microvesicles, exosomes and growth factors which promote cell proliferation and cell biological motility maintenance [61][62][63]. It was reported that EPCs derived exosomes transplantation signi cantly accelerate bone regeneration in rats [37].…”