VEGF gene therapy for the survival of transplanted fat tissue in nude mice

The objective of this study was to determine the effects of adenovirus-mediated vascular endothelial growth factor (Ad-VEGF) on the angiogenesis and survival of free-fat tissue transplantation in nude mice. Thirty 6-week-old CD-1 nude male mice were injected with 1ml fat tissue (harvested by suction-assisted lipectomy from the breast of humans) in the subcutaneous of scalp and were randomised into three groups of 10 animals each. Group 1 was the study group, in which Ad-VEGF was mixed with transplanted fat tissue and injected into mice. In group 2, adenovirus-mediated green fluorescent protein (Ad-GFP) gene was mixed with transplanted fat tissue and injected into the mice. In group 3, normal saline alone was used. Both group 2 and group 3 are control groups. The animals were euthanised 15 weeks after the procedure. The fat survival weight and volume of the study group were significantly greater than those of two control groups (p<0.05). Light microscopical examination of haematoxylin and eosin-stained slides of the dissected fat 15 weeks after injection was performed in group 1 and group 2. Less cyst formation and fibrosis, indicating improved quality of the injected fat, can be obtained by the addition of Ad-VEGF. Vascular density was evaluated at the microvascular level through the use of light microscopic sections of the central part of the fat tissue at 15 weeks after injection by von Willebrand factor staining. Histological evaluation showed that capillary density increased markedly in the study group mice. Mice of the study group disclosed significantly higher VEGF protein levels detected by ELISA assay of plasma samples obtained from the mice after the fat injection (day 1, 4, 7 and 28; p<0.01) at each time point than the mice of the two control groups. The findings reported in this study indicate that the VEGF gene therapy can enhance the survival and the quality of grafted fat tissue, which may be due to induction of angiogenesis.