Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Angiogenesis: Potencial Clinical Application

Abstract

Mesenchymal stem cells (MSCs) are adult multipotent stem cells that are able to differentiate into multiple specialized cell types including osteocytes, adipocytes, and chondrocytes. MSCs exert different functions in the body and have recently been predicted to have a major clinical/therapeutic potential. However, the mechanisms of self-renewal and tissue regeneration are not completely understood. It has been shown that the biological effect depends mainly on its paracrine action. Furthermore, it has been reported that the secretion of soluble factors and the release of extracellular vesicles, such as exosomes, could mediate the cellular communication to induce cell-differentiation/self-renewal. This review provides an overview of MSC-derived exosomes in promoting angiogenicity and of the clinical relevance in a therapeutic approach.

Protective Role of Stem Cell Derived Extracellular Vesicles in an In Vitro Model of Hyperglycemia-Induced Endothelial Injury

“…This confirms that ASC and MSC EVs have both pro-angiogenic properties [11,24] and are able to restore tube formation ability in endothelial cells damaged by high glucose conditioning. These biological effects are consistent with previous observation that MSC EVs and ASC EVs contain several proangiogenic factors [11][12][13][14][24][25][26][27] and miRNAs [20][21][22]46]. …”

“…EVs have been suggested to transfer several paracrine signaling molecules, such as immunomodulators, angiogenic factors, antiapoptotic factors, antioxidants molecules, and cellular chemotaxis inducers [11]. Recent studies showed that EVs derived from MSC (MSC EVs) contain vascular endothelial growth factor (VEGF), transforming growth factor β1 (TGFβ1), interleukin 8 (IL-8) [12,13], hepatocyte growth factor (HGF) [14][15][16], HES Family BHLH transcription factor 1 (HES1) [17], and human T-cell factor 4 (TCF4) [18,19], but also miRNA stimulating angiogenesis, such as miR210, miR-126, miR-132, miR-21 [20], miR-222, let-7f [21,22], and cell-cycle progression and proliferation, such as miR-191, miR-222, miR-21, let-7a [21,22].…”

“…These factors induce survival, proliferation, and proangiogenic signaling in recipient endothelial cells [11]. Adipose-derived stem cells (ASC) are mesenchymal stem cells with self-renewal property and multipotent differentiation, such as adipogenesis, osteogenesis, and chondrogenesis.…”

Anti‐inflammatory effects of hypoxia‐preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: a key role of IL‐37

“…A large body of evidence suggests that paracrine mechanisms mediated by soluble factors that are released from MSCs play an important role in improving disease progression (11–13). Upon receiving pathologic signals, like inflammatory signals, these bioactive factors are homed to the site of injury, where they inhibit proinflammatory responses, prevent apoptosis, and induce tissue-specific precursor cell differentiation (14). …”

Vascular precursor cells in tissue injury repair

“…Like EPCs, MSCs produce extracellular vesicles to promote migration and angiogenic activity of endothelial cells and pericytes 252,253 . Activities of MSC-derived extracellular vesicles in promoting neovascularization as well as the potential of their application for clinical treatment have been comprehensively discussed in a recent review article 254 .…”