Lymphatic Vessel–Mediated Attenuation of Persistent Macrophage Infiltration Improves Fat Grafting Outcomes in Mice Models

Abstract

Abstract Background Persistent macrophage infiltration may lead to adverse consequences, such as calcifications and nodules in fat grafts. Lymphatic vessels, which transport inflammatory cells, are involved in regulating inflammatory responses. Less is known, however, about lymphatic vessels after fat grafting. Objectives The aim of this study was to explore the regulation of fat graft survival by lymphatic vessels. Methods A common adipose graft model was constructed to assess the processes responsible for changes in the number of lymphatic vessels in grafts. Adipose tissue samples from C57/BL6 mice and green fluorescent protein–expressing mice were cross-grafted to determine the source of lymphatic vessels. The number of lymphatic vessels in the grafts was increased by treatment with vascular endothelial growth factor C, and the effects of this increase on fat grafting were evaluated. Results The number of lymphatic vessels was greater in postgrafted fat than in inguinal fat before transplantation, with lymphatic vessels in these grafts gradually transitioning from donor to recipient sources. Lymphatic vessels grew more slowly than blood vessels during early stages of grafting; during later stages, however, the number of blood vessels declined markedly, with more lymphatic vessels than blood vessels being observed 60 days after grafting. Vascular endothelial growth factor C treatment increased graft lymphatics and distant volume retention, while reducing fibrosis and oil sacs. Lymphatic vessels acted as drainage channels for macrophages, with the degree of sustained macrophage infiltration decreasing with increases in the number of lymphatic vessels. Conclusions Increasing the number of lymphatic vessels is beneficial for fat graft survival, which may be related to a reduction in prolonged macrophage infiltration. Level of Evidence: 4