Abstract
Recently, many studies investigated the role of a specific type of stem cell named the endothelial progenitor cell (EPC) in tissue regeneration and repair. EPCs represent a heterogeneous population of mononuclear cells resident in the adult bone marrow. EPCs can migrate and differentiate in injured sites or act in a paracrine way. Among the EPCs’ secretome, extracellular vesicles (EVs) gained relevance due to their possible use for cell-free biological therapy. They are more biocompatible, less immunogenic, and present a lower oncological risk compared to cell-based options. EVs can efficiently pass the pulmonary filter and deliver to target tissues different molecules, such as micro-RNA, growth factors, cytokines, chemokines, and non-coding RNAs. Their effects are often analogous to their cellular counterparts, and EPC-derived EVs have been tested in vitro and on animal models to treat several medical conditions, including ischemic stroke, myocardial infarction, diabetes, and acute kidney injury. EPC-derived EVs have also been studied for bone, brain, and lung regeneration and as carriers for drug delivery. This review will discuss the pre-clinical evidence regarding EPC-derived EVs in the different disease models and regenerative settings. Moreover, we will discuss the translation of their use into clinical practice and the possible limitations of this process.
Highlights
In recent years, the use of adult stem cells has progressively been extended to methods and protocols for tissue regeneration and repair
The results demonstrated that endothelial progenitor cell (EPC) and EPC-extracellular vesicles (EVs) injection ameliorated vascular geometry, proliferation, and hemodynamic function compared to the control [43]
Glomerulonephritis is a renal disease in which glomerular inflammation is determined by a wide range of immune-mediated disorders that can lead to acute kidney injury or gradually progress to chronic renal failure [56]
Summary
The use of adult stem cells has progressively been extended to methods and protocols for tissue regeneration and repair. EPCs represent a heterogeneous population of resident mononuclear cells that originate in the bone marrow [1] They are CD34-positive cells and were isolated for the first time in 1997 by Asahara and coworkers from peripheral blood circulation using magnetic microbeads [2]. EPCs appear in culture after 3–5 days and are obtained through a negative selection on fibronectin-coated plates These cells display a round shape, a slow proliferation rate, and secrete angiogenic factors contributing to neovascularization [6]. The study of EV biology is an expanding research field because of EVs’ potential as therapeutic tools for treating various diseases, including neurodegeneration, cardiovascular dysfunction, and cancer Their classification is continuously evolving, EVs can be divided into three main types: exosomes, microvesicles, and apoptotic bodies [11]. According to the recent findings in the literature, we will discuss potential therapeutic strategies based on the application of EPC-derived EVs to promote tissue regeneration in different diseases
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