Objective: To construct a burn model of early and midterm human Foetal Skin (hFS) in vitro, to observe its morphological and histological changes after transplantation, and to examine the expression of Matrix Metalloproteinases (MMPs) and Tissue Inhibitors of Metalloproteinases (TIMPs), and further to analyse their roles in foetal wound healing preliminarily.
Methods: hFS harvested from aborted foetuses (gestational age 14-24 weeks) was transplanted into the backs of nude mice. Four weeks later, a burn wound was made in the transplanted foetal skin with a thermostatic electrical scald apparatus. To examine the role of exogenous mature immune cells, human Peripheral Blood Mononuclear Cells (hPBMCs) were injected into the subcutaneous layer of transplanted hFS. The histological characteristics and the expression of MMP-2, MMP-7, MMP-9, and TIMP-1 were examined during the wound-healing process above.
Results: The transplanted foetal skin survived on the backs of mice, the burn wounds healed rapidly and without scarring, and skin appendages regenerated after the epidermis were repaired. Injection of hPBMCs prolonged the burn wound-healing process and caused obvious scarring. MMP-2 expression was observed in the surviving grafts, but MMP-7 expression was not observed throughout the normal growth process after transplantation. MMP-7 expression was observed around the burn wound, but MMP-2 expression was observed only in surviving follicles. MMP-9 expression was observed in the cytoplasm of deep epithelial cells of skin appendages. TIMP-1 expression level was slightly lower than that of MMP-9, although its pattern of expression was similar to that of MMP-9. Injection of exogenous mature immune cells (hPBMCs) into the burn injury changed the patterns of MMP-9 and TIMP-1 expression.
Conclusion: Our method for constructing an early or midterm hFS burn model is simple and reliable. HFS maintains the ability for scarless wound healing and regeneration when transplanted into nude mice. This new animal model may be suitable for investigating the mechanisms responsible for hFS wound healing. Injection of hPBMCs prolonged burn wound healing and caused the formation of scars in the wound. MMPs and TIMPs expression might be important factors for scarless wound healing.