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Improvement of the Survival of Human Autologous Fat Transplantation by Using VEGF-Transfected Adipose-Derived Stem Cells

Lu, Feng M.D., Ph.D.; Li, Jie M.D.; Gao, JianHua M.D., Ph.D.; Ogawa, Rei M.D., Ph.D.; Ou, Chunquan Ph.D.; Yang, Bo M.D., Ph.D.; Fu, Bingchuan M.D.

Plastic & Reconstructive Surgery: November 2009 - Volume 124 - Issue 5 - pp 1437-1446
doi: 10.1097/PRS.0b013e3181babbb6
Experimental: Original Articles
Discussion

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).

Conclusion: Adipose-derived stem cells together with VEGF transduction can enhance the survival and quality of transplanted fat tissues.

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.

Received for publication November 14, 2008; accepted April 9, 2009.

Feng Lu and Jie Li contributed equally to the research and should be viewed as co-first authors.

Disclosure: None of the authors has a financial interest to declare in relation to the content of this article.

JianHua Gao, M.D., Ph.D. Department of Plastic and Reconstructive Surgery; Nanfang Hospital; Southern Medical University; 510515 Guangzhou, China; gaopsnf@yahoo.com.cn

©2009American Society of Plastic Surgeons