Histological Evaluation of Experimentally Induced Critical Size Defect Skin Wounds Using Exosomal Solution of Mesenchymal Stem Cells Derived Microvesicles

Abstract

Background and ObjectivesThe present study investigated whether MSCs derived microvesicles (MVs) or (Exosomes) can exert therapeutic effects on an experimental model of cutaneous injury and explored the underlying involving mechanisms.Methods and ResultsThree bilateral full thickness circular wounds were created on the back of two groups of dogs using 2-cm dermal punch. The wounds were at least 2.5 cm apart. Saline was subcutaneously injected in 4 places around each wound area in group-I (control), whereas an equal volume of exosomal solution of MSCs derived MVs was similarly injected in group-II. The findings demonstrated that MSCs derived MVs had significantly promoted cutaneous wound healing, collagen synthesis, and vascularization at wound sites. The application of the exosomal solution had not only promoted the generation of newly formed vessels, but also have accelerated their development and maturation leading to a faster healing process.ConclusionsMSC-Exosomes appeared to be a superior candidate for treating cutaneous wounds than their originator cells, and may represent a promising opportunity to develop a novel cell-free therapy approach that might overcome the obstacles and risks associated with the use of native or engineered stem cells transplantation therapy.

Exosomes Secreted from Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells Accelerate Skin Cell Proliferation

“…Recent studies suggest that cells transmit biomolecules to other cells through the luminal cargo and membrane molecules present in the exosomes [ 25 ]. From a translational viewpoint, exosomes secreted from MSCs have shown promising therapeutic effects in a wide range of preclinical models of tissue repair, including kidney, liver, lung, myocardial infarction, cerebral artery occlusion, and skin wound healing [ 26 , 27 ]. Zhang et al [ 28 ] showed that the exosomes from iMSCs accelerated the process of wound repair by enhancing collagen synthesis and vessel formation and through the stimulation of proliferation and migration of HDFs and human umbilical vein endothelial cells (HUVECs).…”

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

“…The works published at the time of writing were less than 50, and there is much to know about the practical clinical application of this therapeutic strategy. Yet, such published papers show that the EV derived from the MSC may positively modulate the different phases of the wound-healing process, as it has been proven by histological evaluations in animal models, including dogs (El-Tookhy et al, 2017).…”

Veterinary Regenerative Medicine for Musculoskeletal Disorders: Can Mesenchymal Stem/Stromal Cells and Their Secretome Be the New Frontier?

“…As expected, photographs and histopathological evaluation showed better and faster endpoints of the healing process in dogs treated with exosomes, in particular about the formation of extracellular matrix, angiogenesis, and re-epithelization. The findings underline the efficacy and safety of cell-free therapy in wound repair, paving the way for future new therapy approach that overcome the limitations associated with the use of cells implantation [116].…”