Cai Junrong, Li Bin, Liu Kaiyang, Li Guanghui, Lu Feng
Department of Plastic and Cosmetic Surgery, Nanfang Hospital, Southern Medical University, Guang Zhou, Guang Dong, PR China.
Zunyi Medical University, 201 Dalian Rd, Huichuan Qu, Zunyi, Guizhou, PR China.
Biochem Biophys Res Commun. 2017 Aug 19;490(2):560-566. doi: 10.1016/j.bbrc.2017.06.078. Epub 2017 Jun 15.
Fat grafting experiences a regeneration process from free lipoaspirate to intact adipose tissue. The adipose extracellular matrixes (ECM) provide the structure and biochemical support for surrounding cells; inflammatory cells, like macrophages, regulate the process. Our hypothesis states that transferred fat undergoes ECM remodeling after fat grafting and this process is regulated by macrophage infiltration.
Lipoaspirate was injected subcutaneously into the back of nude mice. The micro-structure of the fat grafts was observed and evaluated using scanning electron microscope (SEM) and collagen I immunohistostaining. The gene transcription level of collagen proteins and the matrix metalloproteinases (MMPs) were assessed by qRT-PCR. Local injection of clodronate-encapsulated liposome was used to evaluate the role of macrophages of fat grafts at different stages in ECM remodeling, depletion of macrophages, at different time points (Week 1 and Week 4).
Results from the SEM analysis showed that liposuction caused severe damage to the ECM structure in freshly aspirated adipose tissue. On Day 1 post-transplantation, the surface of adipocytes was covered with platelets and this secreted fibrin network on the fat grafts. An integral adipose structure was already established with an intact ECM at the end of Week 1. The early depletion of macrophages remarkably hindered ECM reconstruction process by down-regulating the expression of collagen proteins and MMPs. Expression of Collagen I was significantly decreased after depletion of macrophages in both gene and protein levels. Results also showed that the depletion of macrophages at the later stage of fat grafting resulted in less fibrosis and capsule formation.
Free fat aspirates undergo a prompt ECM reconstruction process and completed in the first week; this process can be initiated with platelets and mainly modulated by inflammatory cells such as macrophages. It was also observed that prolonged macrophage infiltration contributes to fibrosis and capsule formation in fat grafts.
脂肪移植经历了从游离脂肪抽吸物到完整脂肪组织的再生过程。脂肪细胞外基质（ECM）为周围细胞提供结构和生化支持；炎症细胞，如巨噬细胞，调节这一过程。我们的假设是，移植后的脂肪会经历ECM重塑，且这一过程受巨噬细胞浸润调节。
将脂肪抽吸物皮下注射到裸鼠背部。使用扫描电子显微镜（SEM）和I型胶原免疫组化观察并评估脂肪移植的微观结构。通过qRT-PCR评估胶原蛋白和基质金属蛋白酶（MMPs）的基因转录水平。在不同时间点（第1周和第4周）局部注射氯膦酸盐包裹的脂质体，以评估脂肪移植不同阶段巨噬细胞在ECM重塑中的作用，即巨噬细胞的清除。
SEM分析结果显示，吸脂对新鲜抽吸的脂肪组织中的ECM结构造成严重破坏。移植后第1天，脂肪细胞表面覆盖有血小板，血小板在脂肪移植部位分泌纤维蛋白网络。在第1周结束时，已形成具有完整ECM的完整脂肪结构。巨噬细胞的早期清除通过下调胶原蛋白和MMPs的表达显著阻碍了ECM重建过程。巨噬细胞清除后，I型胶原在基因和蛋白水平的表达均显著降低。结果还表明，在脂肪移植后期清除巨噬细胞会导致较少纤维化和包膜形成。
游离脂肪抽吸物会迅速经历ECM重建过程，并在第一周内完成；这一过程可由血小板启动，主要由巨噬细胞等炎症细胞调节。还观察到，巨噬细胞的长期浸润会导致脂肪移植中的纤维化和包膜形成。
