Department of Plastic and Cosmetic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Kaohsiung J Med Sci. 2022 Sep;38(9):889-896. doi: 10.1002/kjm2.12570. Epub 2022 Jul 14.
Fat transplantation is widely used for soft-tissue filling and wound repair. Owing to the biological changes in adipocytes in some metabolic diseases, allograft fat can provide a better source of donor fat than autologous fat. Fingolimod (FTY720) possesses a powerful immunomodulatory function. This study aimed to investigate the protective effect of FTY720 in allogeneic fat transplantation. C57BL/6J mice that received allografts were randomly divided into two groups and treated with saline and FTY720, respectively. Fat graft samples were obtained at 1, 6, and 20 weeks posttransplantation. Graft volumes, graft structure, and immune cells were estimated using histological examination, immunohistochemistry, staining immunofluorescence (IF), and quantitative real-time polymerase chain reaction (qRT-PCR). Inflammatory cytokine mRNA expression in grafts was detected by qRT-PCR. FTY720 treatment significantly enhanced allograft retention, structural integrity, and neovascularization, thereby demonstrating the potential of FTY720 in improving graft survival. Further IF staining showed that FTY720 increased regulatory T cell infiltration and reduced macrophage infiltration to some extent. FTY720 treatment also enhanced the expression of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10 and weakened the expression of the pro-inflammatory cytokines TNF-α and IL-6. Furthermore, FTY720 treatment upregulated the expression of CD31 positive cells. This study demonstrated the potential efficacy of FTY720 in improving the graft survival rate of syngeneic fat allograft models, possibly by suppressing immune rejection and promoting angiogenesis. Therefore, this study offers key insights into the potential application of a drug-assisted strategy to prolong allograft fat survival.
脂肪移植广泛用于软组织填充和伤口修复。由于一些代谢疾病中脂肪细胞的生物学变化,同种异体脂肪可以提供比自体脂肪更好的供体脂肪来源。芬戈莫德(FTY720)具有强大的免疫调节功能。本研究旨在探讨 FTY720 在同种异体脂肪移植中的保护作用。接受同种异体移植物的 C57BL/6J 小鼠被随机分为两组,分别用生理盐水和 FTY720 处理。在移植后 1、6 和 20 周时获取脂肪移植物样本。通过组织学检查、免疫组织化学、染色免疫荧光(IF)和定量实时聚合酶链反应(qRT-PCR)评估移植物体积、移植物结构和免疫细胞。通过 qRT-PCR 检测移植物中炎性细胞因子的 mRNA 表达。FTY720 治疗显著增强了同种异体移植物的保留、结构完整性和新生血管形成,从而证明了 FTY720 改善移植物存活的潜力。进一步的 IF 染色表明,FTY720 增加了调节性 T 细胞的浸润,并在一定程度上减少了巨噬细胞的浸润。FTY720 治疗还增强了抗炎细胞因子白细胞介素(IL)-4 和 IL-10 的表达,并减弱了促炎细胞因子 TNF-α和 IL-6 的表达。此外,FTY720 治疗上调了 CD31 阳性细胞的表达。本研究表明,FTY720 有可能通过抑制免疫排斥和促进血管生成来提高同种异体脂肪移植物模型的移植物存活率。因此,本研究为药物辅助策略延长同种异体脂肪存活的潜在应用提供了关键见解。