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ORIGINAL RESEARCH ARTICLE

Revascularization Determines Volume Retention and Gene Expression by Fat Grafts in Mice

Motoko Yamaguchi^*, Fumiaki Matsumoto^*, Hideaki Bujo^,1, Manabu Shibasaki, Kazuo Takahashi, Shinya Yoshimoto^*, Masaharu Ichinose^* and Yasushi Saito

^* Department of Plastic, Reconstructive and Esthetic Surgery (J4), Department of Genome Research and Clinical Application (M6), and Department of Clinical Cell Biology (F5), Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan

To whom requests for reprints should be addressed at ¹ Department of Genome Research and Clinical Application (M6), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. E-mail: hbujo{at}faculty.chiba-u.jp

Autologous fat transplantation is a popular and useful technique in plastic and reconstructive surgery. The efficiency and survival of such grafts is predictable in many cases, but there are still issues to be resolved, such as how to improve graft volume retention. To address the issue of volume retention, we studied the effect of revascularization from the recipient on the size and function of adipocytes in fat grafts. Treatment of mice with TNP-470, an angiogenesis inhibitor, reduced blood flow from the recipient into the graft after subcutaneous transplantation of epididymal fat. The weight of transplanted tissues and the size of adipocytes in the grafts were significantly lower in mice treated with TNP-470 (TNP mice) than in control mice. Expression of genes for enzymes related to lipid accumulation was decreased in the grafts of TNP mice compared with control mice. Moreover, the expression of adipocyte-derived angiogenic peptides, VEGF and leptin, was significantly lower in the grafts of TNP mice than in grafts from control animals. The expression of VEGF and leptin by cultured human adipocytes was increased in the presence of conditioned medium from cultured vascular endothelial cells. These results show that the inhibition of the revascularization of fat grafts after transplantation reduces graft volume retention and cellular function. Early and adequate revascularization may be important for both the supply of nutrients and vasoactive interactions between vascular endothelial cells and adipocytes in graft.

Key Words: fat transplantation • TNP-470 • revascularization • lipid • VEGF • leptin