Intradermal injection of GFP-producing adipose stromal cells promotes survival of random-pattern skin flaps in rats

Abstract

Background Tissue necrosis is a common complication in operations that use skin flaps for reconstructive surgery. Here we demonstrate the beneficial effect of autologous genetically modified adipose-derived stromal cells (ASCs) in the survival of random-pattern skin flaps. Methods ASCs were isolated from the inguinal fat pad of Wistar rats and genetically modified in order to permanently produce green fluorescent protein (GFP) using the Sleeping Beauty transposon technology. Autologous GFP-producing cells were then injected intradermally into random-pattern skin flaps planned on the dorsal area of rats. Results Injection of ASCs resulted in significant improvement of skin flap survival. Histological analysis showed that the connective tissue was almost intact in skin flaps treated with ASCs in contrast to disorganized tissues from mocktreated skin flaps. GFP ASCs were detected in the endothelium of blood vessels co-expressing the endothelial marker von Willebrand factor, thus suggesting that they promote blood vessel regeneration. Conclusions These findings indicate that transplantation of autologous GFP ASCs improve survival of skin flaps. This methodology suggests that the use of genetically modified ASCs producing, e.g., angiogenic factors may facilitate survival and integration of flaps in plastic surgery.