Vascular Functional Recovery and Reparation by Human Endothelial Progenitor Cells

Abstract

Endogenous vascular reparation is based on mobilization, differentiation, and proliferation of bone marrow–derived and resident proangiogenic endothelial precursors, which directly and indirectly participate in adaptive and maladaptive vascular remodeling processes. The endothelial progenitor cells (EPCs) being under epigenetic control, metabolic stimuli, and paracrine/autocrine regulation frequently demonstrate a weak ability to survival and lowered potency to migration and proliferation among patients with known cardiovascular disease. This phenomenon is known as EPC dysfunction, which is in the core of an altered endogenous repair system. Lowered levels and impaired functional abilities in both resident and circulating endothelial progenitors are considered crucial contributors of vascular remodeling and endothelial dysfunction, which are central players in the development and progression of atherosclerosis, arterial and pulmonary hypertension, myocardial infarction, and heart failure. Although there is wide-range evidence of the fact that injections of exogenous bone marrow–derived proangiogenic endothelial precursors do not engraft into impaired vessels, but that such circulating EPCs may regulate vascular repair through several paracrine mechanisms and thereby attenuate clinical condition of the patients and possibly improve prognosis. The circulating secretome and extracellular vesicles released by the EPCs contain various proangiogenic factors (active peptides, lipids, transforming growth factor-beta, bone morphogenetic protein-2, matrix metalloproteinases, chromatin, and noncoding RNAs) that are crucial for spontaneously formed organized cell clusters to support proliferative response in surrounding tissues. Additionally, EPCs secretome maintains angiogenesis, neovascularization, immune response, and inflammation in injured vasculature. Previously supply of exogenous proliferative EPCs had been derived from various pluripotent stem cells such as embryonic stem cells or induced pluripotent stem cells, but so far they can be constructed from individual’s reprogrammed fibroblasts and this procedure did not require inducing pluripotency and had lowered teratogenic risk. Moreover, there are great opportunities to stimulate resident EPCs to (trans)-differentiation and proliferation by exogenous extracellular vesicles embarked on appropriate active molecules and noncoding RNAs. Overall, the concept of support of vascular reparation through engrafting EPCs appears to be promising. The chapter depicted previous evidence of mechanisms of regulation of vascular repair by residence regenerative vascular cells and results of preclinical and clinical studies for vascular functional recovery and reparation by EPCs and extracellular vesicles.