Abstract
The cells secrete extracellular vesicles (EV) that may have an endosomal origin, or from evaginations of the plasma membrane. The former are usually called exosomes, with sizes ranging from 50 to 100 nm. These EV contain a lipid bilayer associated to membrane proteins. Molecules such as nucleic acids (DNA, mRNA, miRNA, lncRNA, etc.) and proteins may be stored inside. The EV composition depends on the producer cell type and its physiological conditions. Through them, the cells modify their microenvironment and the behavior of neighboring cells. That is accomplished by transferring factors that modulate different metabolic and signaling pathways. Due to their properties, EV can be applied as a diagnostic and therapeutic tool in medicine. The mesenchymal stromal cells (MSC) have immunomodulatory properties and a high regenerative capacity. These features are linked to their paracrine activity and EV secretion. Therefore, research on exosomes produced by MSC has been intensified for use in cell-free regenerative medicine. In this area, the use of EV for the treatment of chronic skin ulcers (CSU) has been proposed. Such sores occur when normal healing does not resolve properly. That is usually due to excessive prolongation of the inflammatory phase. These ulcers are associated with aging and diseases, such as diabetes, so their prevalence is increasing with the one of such latter disease, mainly in developed countries. This has very important socio-economic repercussions. In this review, we show that the application of MSC-derived EV for the treatment of CSU has positive effects, including accelerating healing and decreasing scar formation. This is because the EV have immunosuppressive and immunomodulatory properties. Likewise, they have the ability to activate the angiogenesis, proliferation, migration, and differentiation of the main cell types involved in skin regeneration. They include endothelial cells, fibroblasts, and keratinocytes. Most of the studies carried out so far are preclinical. Therefore, there is a need to advance more in the knowledge about the conditions of production, isolation, and action mechanisms of EV. Interestingly, their potential application in the treatment of CSU opens the door for the design of new highly effective therapeutic strategies.
Highlights
Extracellular Vesicles: Definition, Discovery, Classification, Isolation, and CharacterizationThe word “exosome” is ambiguous, requiring clarification
The exosome vesicles are a type of extracellular vesicles (EV), which are defined as lipidbilayer spheroid structures, without replicating capacity, that are released from cells, including both prokaryotes and eukaryotes
Due to the interest and multiple studies available about the clinical applications of the exosomes derived from mesenchymal stromal cells (MSC), the main objective of the present work is to show a critical review about their therapeutic properties, including their specific applications for the treatment and healing of skin ulcers
Summary
Extracellular Vesicles: Definition, Discovery, Classification, Isolation, and Characterization. Since the discovery that EV carry nucleic acids (Ratajczak et al, 2006; Valadi et al, 2007), numerous studies have described the presence of different RNA types in such particles They include messenger RNA (mRNA), miRNA, and non-coding RNA (ncRNA). Activating membrane receptors through proteic or lipidic ligands, as well as pouring their contents into receptor cells (Figure 2) This way, they can transfer transcription factors, oncogenes, miRNA, mRNA, and even infectious particles (Yáñez-Mó et al, 2015). The physiological roles of the EV depend on their cargos and their capacity to transfer proteins, nucleic acids, and other molecules into the receptor cells They can be intravenously given to patients, having the capacity to pass through the blood–brain barrier. Due to the interest and multiple studies available about the clinical applications of the exosomes derived from MSC, the main objective of the present work is to show a critical review about their therapeutic properties, including their specific applications for the treatment and healing of skin ulcers
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