人脂肪干细胞胞外囊泡携miR-423-5p促进脂肪移植物中M2型巨噬细胞极化的分子机制研究

脂肪移植是目前软组织填充的首选方案，但较低的体积保留率限制其推广。前期研究发现，人脂肪干细胞胞外囊泡（hASC-EVs）可通过诱导巨噬细胞的M2型极化来促进脂肪移植后的组织新生并提高体积保留率。预实验进一步发现，其机制与hASC-EVs向巨噬细胞传递miR-423-5p靶向抑制SOCS3的转录密切相关。但miR-423-5p对SOCS3及下游JNK-STAT通路的调控机制尚不明确，难以干预脂肪移植后的体积保留率。因此，提出假说：hASC-EVs在脂肪移植物中向巨噬细胞传递miR-423-5p, 靶向调控SOCS3/JNK-STAT信号通路诱导巨噬细胞M2型极化，提高脂肪移植体积保留率。本研究拟围绕该假说，采用miRNA模拟物构建，基因敲除，基因沉默等方法，重点研究miR-423-5p对巨噬细胞中SOCS3/JNK-STAT通路的调控机制，进而为开发新药，提高脂肪移植体积保留率提供实验基础。

Fat grafting is the first choice for soft tissue filling at present, but the low volume retention rate limits its clinical application. Previous studies demonstrated that extracellular vesicles of human adipose-derived stem cells (hASC-EVs) promote tissue regeneration and increase volume retention of fat grafts by inducing M2 polarization of macrophages. In the pre-experiment, it was further demonstrated that the mechanism was closely related to the transfer of miR-423-5p from hASC-EVs to macrophages to inhibit the transcription of SOCS3. However, the regulatory mechanism of miR-423-5p on SOCS3 and downstream JNK-STAT pathway is not clear, so it is difficult to interfere with the volume retention after fat transplantation. Therefore, it is hypothesized that hASC-EVs transmit miR-423-5p to macrophages in fat grafts and regulate the SOCS3/JNK-STAT signal pathway to induce M2 polarization of macrophages and to improve the volume retention of fat grafts. Based on this hypothesis, this study focuses on the regulatory mechanism of miR-423-5p on SOCS3/JNK-STAT pathway in macrophages by process of miRNA mimic construction, gene knockout and gene silencing, etc., so as to provide a research basis for developing new drugs and improving the volume retention rate of fat grafting.