The Role of Mesenchymal Stem Cell Derived Exosomes versus Melatonin on Skin Wound Healing of Adult Male Albino Rats: Histological Study

Background: Wound healing involves interaction of growth factors and cytokines to restore tissue integrity. Melatonin and MSC-derived exosomes have anti-inflammatory effect, enhance re-epithelization, angiogenesis and regulate collagen remodeling. Aim of the Work: To assess melatonin effect versus MSC-derived exosomes in skin wound healing. Materials and Methods: 28 male albino rats were separated equally into 4 groups: Group I (control) left unwounded. Other groups, full-thickness dermal circular wounds were created. Group II, wound left untreated. Group III (melatonin-treated), melatonin was dissolved in saline and given orally in a dose of 5 mg/kg once daily for 14 days. Group IV (exosomes-treated), exosomes were injected once subcutaneously at four sites around wound at a dose of 200 μg MSC-exosomes in 200 μl PBS. After 14 days, skin sections were examined histologically (by light and electron microscopes). Results: Histological and ultrastructural examination of group I was similar to normal skin histological structure. The H&E stained sections from group II indicated a disruption in the outer layer of skin at the wound site, along with a significant presence of inflammatory cells and the new blood vessels formation. Additionally, the masson stained sections revealed thin and disordered collagen fibers in the deeper layer of skin. Electron microscopy analysis of skin slices from group II revealed the absence of hemidesmosomal junctions, along with disruption to the basement membrane and cell-to-cell junctions loss mediated by desmosomes. Both melatonin and MSC-derived exosomes succeeded in restoration of normal histological structure of skin at wound site with more improvement in exosomes treated group . Conclusion: Melatonin and MSC-derived exosomes have ameliorative effect in skin wound healingKeywords: Mesenchymal Stem Cell; Exosomes; Melatonin Skin Wound Healing.