Adenovirus E4+ Endothelial Cells Improve Volume Retention of Transplanted Fat
Ishani D. Premaratne, BA, Mariam Gadjiko, BA, Xue Dong, MD PhD, Jason A. Spector, MD.
Weill Cornell Medicine, New York, NY, USA.
BACKGROUND: The inability of transplanted fat to garner a sufficient blood supply is a key factor in the significant and unpredictable degree of volume loss often seen in autologous fat transplantation. We hypothesized that augmenting the angiogenic milieu of transplanted fat would serve as a powerful means of addressing this problem. E4 cells, which are human endothelial cells (ECs) that have been transduced with the E4ORF1 region of human adenovirus Type 5 (AdE4+EC), are one solution towards improving the angiogenic milieu, as they have been shown to elaborate angiogenic cytokines. Herein we study the potential for E4-enriched fat grafts to demonstrate improved volume retention of transplanted fat in a mouse model.
METHODS: Fifteen nude mice were utilized in order to study volume retention in three experimental groups: “high” AdE4+ EC concentration (1.0 x 106/0.2 mL)-enriched fat grafts, “low” AdE4+ EC concentration (2.5 x 105/0.2 mL)-enriched fat grafts, and control fat grafts (no AdE4+EC) admixed with phosphate-buffered saline (PBS). Each mouse received two identical 500µL fat grafts. These were prepared by admixing 400µL of patient lipoaspirate with 100µL of AdE4+ ECs or PBS and injected percutaneously with a 1cc syringe into the bilateral dorsal subcutaneous areas. Grafts were explanted at 180 days.
RESULTS: Volume retention was significantly higher in the “low” AdE4+ EC concentration group (mean volume retention of 59.1%), compared to the control group (27.9%, p = 0.002). There was also a statistically significant difference in percent volume preservation between “high” vs. “low” AdE4+ EC concentration fat grafts (p = 0.0234). The greatest overall volume retention was seen in the “low” AdE4+ EC concentration group (59.1%), compared to the “high” AdE4+ EC concentration (36.6%) and control groups (27.9%). H&E staining confirmed the presence of healthy fat tissue in all groups without evidence of fibrosis. CONCLUSIONS: AdE4+ EC-enriched fat grafts demonstrate greater volume retention at 6 months compared to fat alone. The observation that greater volume preservation was seen in the lower concentration AdE4+ EC-enriched fat graft group suggests that there is an optimal concentration at which angiogenic properties may be maximized, considering the surface area and density of our grafts. As these transgenic cells are currently being investigated in clinical trials for improving bone marrow transplantation, AdE4+ ECs enriched fat transfer represents a potentially significant “off the shelf” option for promoting the survival of a greater fraction of transplanted fat with increased consistency. 
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