Autologous fibroblasts, peripheral blood mononuclear cells, and fibrin glue accelerate healing of refractory cutaneous ulcers in diabetic mice

Am J Transl Res. 2018 Sep 15;10(9):2920-2928. eCollection 2018.

Abstract

Background/aims: We have developed a method to transplant sheets of autologous fibroblasts and peripheral blood mononuclear cells, which are highly angiogenic and regenerative, as treatment against refractory cutaneous ulcers in mice and rabbits. The cell sheets are also sealed with fibrin to further enhance effectiveness.

Methods: Secretion of growth factors from cells incubated with or without fibrin in vitro was assessed by enzyme-linked immunosorbent assays, while angiogenesis and fibroblast migration were assessed by tube formation and scratch assays. Healing of cutaneous ulcers following transplantation of cells was evaluated in mice with diabetes mellitus.

Results: Secretion of vascular endothelial growth factor, hepatocyte growth factor, and transforming growth factor was much higher from cell sheets supplemented with fibrin than from cell sheets only. Accordingly, supernatants from the former enhanced angiogenesis and fibroblast migration in vitro. Cutaneous ulcers treated with fibrin-glued cell sheets also healed more quickly than untreated ulcers or ulcers treated with cell sheets only.

Conclusion: Fibrin-sealed cells accelerate wound healing and microvascularization by supplying growth factors, and thus are promising as treatment against refractory cutaneous ulcers.

Keywords: Fibrin glue; fibroblast; peripheral blood mononuclear cell.