Abstract
ObjectiveAutograft microskin transplantation has been widely used as a skin graft therapy in full-thickness skin defect. However, skin grafting failure can lead to a pathological delay wound healing due to a poor vascularization bed. Considering the active role of adipose-derived stem cell (ADSC) in promoting angiogenesis, we intend to investigate the efficacy of autograft microskin combined with ADSC transplantation for facilitating wound healing in a full-thickness skin defect mouse model.Material and methodsAn in vivo full-thickness skin defect mouse model was used to evaluate the contribution of transplantation microskin and ADSC in wound healing. The angiogenesis was detected by immunohistochemistry staining. In vitro paracrine signaling pathway was evaluated by protein array and Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway, and protein-protein interaction network analysis.ResultsCo-transplantation of microskin and ADSC potentiated the wound healing with better epithelization, smaller scar thickness, and higher angiogenesis (CD31) in the subcutaneous layer. We found both EGF and VEGF cytokines were secreted by microskin in vitro. Additionally, secretome proteomic analysis in a co-culture system of microskin and ADSC revealed that ADSC could secrete a wide range of important molecules to form a reacting network with microskin, including VEGF, IL-6, EGF, uPAR, MCP-3, G-CSF, and Tie-2, which most likely supported the angiogenesis effect as observed.ConclusionOverall, we concluded that the use of ADSC partially modulates microskin function and enhances wound healing by promoting angiogenesis in a full-thickness skin defect mouse model.
Highlights
Wound healing is a remarkably complex, and continuous process consisted of hemostasis and coagulation, inflammation, proliferation, and wound repairing with scar tissue formation [1]
We found both epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) cytokines were secreted by microskin in vitro
Secretome proteomic analysis in a co-culture system of microskin and adipose-derived stem cell (ADSC) revealed that ADSC could secrete a wide range of important molecules to form a reacting network with microskin, including VEGF, interleukin 6 (IL-6), EGF, urokinase plasminogen activator receptor (uPAR), monocyte chemotactic protein-3 (MCP-3), granulocyte colony-stimulating factor (G-CSF), and Tie-2, which most likely supported the angiogenesis effect as observed
Summary
Wound healing is a remarkably complex, and continuous process consisted of hemostasis and coagulation, inflammation, proliferation, and wound repairing with scar tissue formation [1]. Inappropriate management of wound care would result in a negative contribution to the healing process and potential complications, such as delay or nonhealing wounds. Microskin grafting is a method of laying small sheets of the skin graft on the cutaneous wound to enhance wound healing which has been widely used as skin graft therapy in developing countries [2]. There is a limitation of microskin grafting such as lack of neovascularization, keloid scar formation, and failure of transplantation due to poor wound bed and ischemiareperfusion (IR) [3]. Burn surgeons face a considerable challenge as to how to enhance the effectiveness of microskin grafting
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