Improvement of the survival of human autologous fat transplantation by using VEGF-transfected adipose-derived stem cells.
BACKGROUND
The efficacy of autologous fat transplantation is reduced by fat absorption and fibrosis due to fat necrosis. Enhanced transplant neovascularization early after transplantation may reduce these outcomes. The authors asked whether cell and concomitant gene therapy using adipose-derived stem cells transduced with vascular endothelial growth factor (VEGF) improves fat transplant neovascularization and survival.


METHODS
Human adipose-derived stem cells were expanded ex vivo for three passages, labeled with 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine (DiI), and transduced with VEGF or left untransduced. Human fat tissues were then mixed with the DiI-labeled VEGF-transduced adipose-derived stem cells, the DiI-labeled adipose-derived stem cells, the known vascularization-promoting agent insulin, or medium alone, and 18 nude mice were injected subcutaneously with all four preparations, with each of the four designated spots receiving one of these four mixtures in a random fashion. Six months later, transplanted tissue volume and histology were evaluated and neovascularization was quantified by counting the capillaries.


RESULTS
Control transplant survival was 27.1 +/- 8.2 percent, but mixture with the VEGF-transduced and VEGF-untransduced stem cells significantly increased transplant survival (74.1 +/- 12.6 percent and 60.1 +/- 17.6 percent, respectively). Insulin was less effective (37.7 +/- 6.9 percent). Histological analysis revealed both types of transplants consisted predominantly of adipose tissue, unlike the control transplants, and had significantly less fat necrosis and fibrosis. The VEGF-transduced, adipose-derived stem cell-treated transplants had significantly higher capillary density than the other transplants and bore DiI-double-positive and CD31-double-positive cells (i.e., adipose-derived stem cell-derived endothelial cells).


CONCLUSIONS
Adipose-derived stem cells together with VEGF transduction can enhance the survival and quality of transplanted fat tissues.
Lu
Feng
F
Guangzhou, China; Tokyo, Japan; and Boston, Mass. From the Department of Plastic and Reconstructive Surgery, Nanfang Hospital, and Department of Biostatistics, School of Public Health and Tropical Medicine, Southern Medical University; Department of Plastic, Reconstructive, and Aesthetic Surgery, Nippon Medical School; and Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School.
Li
Jie
J
Gao
JianHua
J
Ogawa
Rei
R
Ou
Chunquan
C
Yang
Bo
B
Fu
Bingchuan
B
D000256:Adenoviridae; D017667:Adipocytes / Q000637:transplantation*; D000273:Adipose Tissue / Q000166:cytology / Q000637:transplantation*; D000818:Animals; D015967:Gene Expression Regulation, Viral; D006085:Graft Survival; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000235:genetics; D033581:Stem Cell Transplantation / Q000379:methods*; D014161:Transduction, Genetic; D014162:Transfection; D019076:Transgenes; D014182:Transplantation, Autologous; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A