Autograft microskin combined with adipose-derived stem cell enhances wound healing in a full-thickness skin defect mouse model

Abstract

Objective Autograft 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 methods An 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. Results Co-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. Conclusion Overall, 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. Electronic supplementary material The online version of this article (10.1186/s13287-019-1389-4) contains supplementary material, which is available to authorized users.

Proinflammatory cytokines regulate epidermal stem cells in wound epithelialization

“…Mesenchymal SCs also reduce scar formation by secreting a variety of antifibrotic cytokines, including hepatocyte growth factor, IL-10, and adrenomedullin [53,55]. Adipose-derived SCs and induced pluripotent SCs reduce scar formation in mouse experiments [56,57].…”

3D bioprinting of integral ADSCs-NO hydrogel scaffolds to promote severe burn wound healing

“…Isolation of ADSCs was performed according to our previous report [ 27 ]. Briefly, inguinal subcutaneous fat was collected from Balb/c mice (male, 8 weeks old) and minced into pieces <1 mm in diameter before digestion with 0.1% Type I collagenase (Gibco, 17100017) at 37°C for 45 min.…”

“…In addition, ADSCs have been permitted to be used in clinical and achieved very good surgical outcomes and patient satisfaction in burn wound [ 10 ]. Our previous study showed that ADSCs are likely attributed to paracrine secretion of trophic factors rather than direct differentiation [ 11 ]. However, low cellular retention, survival rate and engraftment after in vivo transplantation have limited translational medicine [ 12 ].…”

Co-culture of ASCs/EPCs and dermal extracellular matrix hydrogel enhances the repair of full-thickness skin wound by promoting angiogenesis

“…In the repair of small-scale skin defects, skin tissue has a strong ability to regenerate. This regenerative ability is achieved by the vascular system around the defect area, which continuously recruits nearby fibroblasts and related bioactive factors for skin repair and provides nutritional support for the repair process [ 8 ]. However, in the case of large-scale skin defects, severe damage to the surrounding vascular system will affect the recruitment of nearby fibroblasts and the transportation of nutrients, resulting in the limitation of the regeneration process of skin tissues and failure to complete the repair of large-scale skin defects [ 9 ].…”