Improved survival of rat ischemic cutaneous and musculocutaneous flaps after VEGF gene transfer

Abstract

When harvesting microsurgical flaps, the main goals are to obtain as much tissue as possible based on a single vascular pedicle and a reliable vascularization of the entire flap. These aims being in contrast to each other, microsurgeons have been looking for an effective way to enhance skin and muscle perfusion in order to avoid partial flap loss in reconstructive surgery. In this study we demonstrate the efficacy of VEGF 165 delivered by an Adeno-Associated Virus (AAV) vector in two widely recognized rat flap models. In the rectus abdominis myocutaneous flap, intramuscular injection of AAV-VEGF reduced flap necrosis by 50%, while cutaneous delivery of the same amount of vector put down the epigastric flap's ischemia by >40%. Histological evidence of neoangiogenesis (enhanced presence of CD31-positive capillaries and alpha-Smooth Muscle Actin-positive arteriolae) confirmed the therapeutic effect of AAV-VEGF on flap perfusion.

Effects of Vascular Endothelial Growth Factor on Survival of Surgical Flaps: A Review of Experimental Studies

“…120 Over the years, various ways of delivering gene therapy have evolved. Among the many ways of VEGF gene therapy, liposomes [64][65][66][67][68][69] and adenoviral vectors 53,71,72,74,121 get the most ensured results. Gene therapy in general, in at least two studies, has been equivalent in outcomes to traditional VEGF protein results.…”

Reliable and Reproducible Murine Models for Commonly Used Abdominal Plastic Surgical Flaps

“…6 The rat TRAM flap model has been used extensively in experimental studies investigating factors that affect flap survival, including ischemia-reperfusion injury, 7 delay procedures 8,9 and ischemic preconditioning 10 as well as the application of vasoactive agents such as nicotine 11 and vascular endothelial growth factor. [12][13][14][15][16] Moreover, these flaps have been employed in investigating possible future clinical applications of the TRAM flap including allotransplantation 17 and secretion of therapeutic proteins after gene transfer. 2 We have developed a mouse TRAM model because there are several advantages of a mouse model when compared with rats: greater genetic characterization; many more genetically-modified mice and many more mouse-specific reagents.…”

Use of gene-modified keratinocytes and fibroblasts to enhance regeneration in a full skin defect

“…A critical limiting factor may be the lack of a functional vascular network in the engineered skin. Induction of revascularization in skin substitutes after transplantation could help to improve survival and regeneration of the bioartificial skin substitutes [4,5]. With the development of cell-based gene transfer techniques [1,6], genetically modified human keratinocytes (Kc) and fibroblasts (Fb) could be used to prepare skin equivalents, which can produce and deliver the desired therapeutic proteins either systemically or locally after transplantation [7,8].…”