Receptor

Mesenchymal stem cell

Microvesicles

Biology

Gene

Regenerative medicine

microRNA

Chemistry

Immunology

Exosome

Stem cell

Microvesicle

Wound healing

Cell biology

Secretion

Biochemistry

Paracrine signalling

Frontiers in Bioengineering and Biotechnology

The cells secrete microvesicles that may have an endosomal origin, or from evaginations of the plasma membrane. The former are referred to as exosomes, with sizes ranging from 50 to 100 nm. These microvesicles contain a lipid bilayer associated with membrane proteins. Molecules such as nucleic acids (DNA, mRNA, miRNA, lncRNA, etc) and proteins are stored inside. The exosome 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, exosomes can be applied as a diagnostic and therapeutic tool in medicine. The MSC haveimmunomodulatory properties and high regenerative capacity. These features are linked to their paracrine activity and microvesicle secretion. Therefore, research on exosomes produced by MSC has been intensified for use in cell-free regenerative medicine. In this area, the use of exosomes 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 exosomes for the treatment of CSU has positive effects, including accelerating healing and decreasing scar formation. This is because the exosomes 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 exosomes. Interestingly, their potential application in the treatment of CSU opens the door for the design of new highly effective therapeutic strategies.

Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing