IGF-1-Expressing Placenta-Derived Mesenchymal Stem Cells Promote Scalding Wound Healing

Abstract

Background: Stem cell-based regenerative therapy is a novel approach to severe damaged skin. Perinatal tissues such as placenta are considered as promising alternatives. The present study aimed to investigate the effect of insulin-like growth factor-1 (IGF-1)-expressing placenta-derived mesenchymal stem cells (hPMSCs) on healing of burn wounds.

Materials and methods: hPMSCs were isolated from human placenta, and IGF-1 was transducted into hPMSCs via lentivirus. Flow cytometry and MTT assay were performed to assess cell apoptosis and viability, respectively. Immunostaining of CK19 and ki67 was for evaluating epithelial differentiation ability and cell proliferation. For in vivo studies, we established a mouse model of scalding and performed local administration of IGF-1-expressing hPMSCs via subcutaneous injection. Wound histology was analyzed with H&E staining. The expression of fibrogenic cytokines was detected by western blot. The production of pro-inflammatory factors was measured by ELISA.

Results: Overexpression of IGF-1 promoted cell proliferation and epithelial differentiation of hPMSCs in vitro and in vivo. Mice with burn injury displayed increased wound contraction and healing rates following treatment with IGF-1-expressing hPMSCs. There was less inflammatory infiltration and reduced collagen disposition in the presence of IGF-1 at the wound site. Administration of IGF-1-expressing hPMSCs suppressed inflammation by decreasing the levels of pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6. Besides, IGF-1 increased VEGF expression, and decreased TGF-β1, collagen I and collagen III expressions in vivo.

Conclusions: IGF-1-expressing PMSCs promotes cell proliferation and epithelial differentiation, inhibits inflammation and collagen deposition, and thus contributes to wound healing.

Keywords: Burn injury; Epithelial differentiation; Insulin-like growth factor-1; Placenta-derived mesenchymal stem cells; Wound healing.