Endothelial Progenitor Cell-Derived Extracellular Vesicles: Potential Therapeutic Application in Tissue Repair and Regeneration

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.

Engagement of the CXCL12–CXCR4 Axis in the Interaction of Endothelial Progenitor Cell and Smooth Muscle Cell to Promote Phenotype Control and Guard Vascular Homeostasis

“…Of note, inflammatory activation of cells with recombinant low-dose TNFα strongly amplified expression and secretion of CXCL12 in SMCs and EPCs. As we have previously observed that EPC-derived microvesicles (MVs, also known as microparticles or extracellular vesicles) alone may modulate key functions of SMCs and as MVs harbor and transfer bioactive substances including chemokines and microRNAs [ 20 , 21 , 22 ], we also evaluated the presence of CXCL12 in MVs. Indeed, a notable amount of CXCL12 could be identified in MVs derived from EPCs (EPC-MV) and SMCs (SMC-MV), indicating that a relevant portion of released CXLC12 is transferred to MVs ( Figure 1 C).…”

Recovery After Stroke: New Insight to Promote Brain Plasticity

“…Beyond the proven beneficial outcomes with the MSCderived EV treatment in experimental animal models of stroke (34)(35)(36)(37)(38)(39), many aspects are yet to be resolved about the production of EVs for their use in clinical practice, such us large-scale production, conditions in different physiologically environments, and standardized experimental protocol for extracting EVs to provide batch uniformity according to GMP regulations (40,48,49).…”

Mesenchymal Stem Cells in Adipose Tissue and Extracellular Vesicles in Ovarian Cancer Patients: A Bridge toward Metastatic Diffusion or a New Therapeutic Opportunity?

“…Moreover, they do not have an oncologic risk or a risk of permanent engraftment or transformation. Finally, their low immunogenic potential allows a possible allogeneic use, making it easier to develop off-the-shelf products [93]. However, the main limitation of the use of ADSC-derived EVs consists in the production upscaling.…”