Compact Fat Grafting: A Novel Method to Improve Graft Retention Through Modulation of Adipocyte Size

Background: The viable zone where adipocytes and/or adipose-derived stem cells survive is present at the surface of graft fat tissue; however, there is controversy regarding the zone thickness. Graft retention could be improved if more adipocytes are included in the zone. Objectives: We hypothesize that a temporary reduction in adipocyte size prior to grafting could increase the number of adipocytes in the viable zone. We reduced the adipocyte size by treatment with MLN4924, which controls lipid accumulation in adipocytes, and investigated the histological and microenvironmental changes in grafted fat. Methods: Subcutaneous fat harvested from wild-type C57BL/6J mice was chopped into small pieces; treated with dimethyl sulfoxide (control group), 0.25 mu M MLN4924, or 0.5 mu M MLN4924 for 4 days; and grafted into recipient C57BL/6J mice at the supraperiosteal plane of the skull. Results: The reduced adipocyte size in response to MLN4924 treatment was restored within 8 weeks after fat grafting. The MLN4924-treated groups exhibited substantially greater graft volume, lower tissue hypoxia, and higher production of M2 macrophages compared with the control group. Conclusions: Grafting with compact fat that had smaller adipocytes improved the microenvironment by modulating tissue hypoxia and macrophage polarization, leading to improved graft retention. Therefore, compact fat grafting may offer a new clinical strategy without the need for stem cell manipulation.N