Aesthet Surg J. 2024 Jun 14;44(7):NP501-NP518. doi: 10.1093/asj/sjae075.
Macrophage-mediated inflammatory response in the early post-grafting period restricts fat graft retention. Pyroptosis is a novel type of programmed cell death that extensively participates in inflammatory pathologies.
This study sought to determine whether macrophage pyroptosis was activated during the inflammatory phase after fat grafting and to investigate the efficacy of a pyroptosis inhibitor, disulfiram (DSF), in fat graft retention.
We established a C57BL/6 mice fat grafting model and then analyzed macrophage pyroptosis. DSF (50 mg/kg, every other day) was intraperitoneally injected starting 1 hour before fat grafting and continued for 14 days. An in vitro co-culture system was established in which mouse RAW264.7 macrophages were co-cultured with apoptotic adipocytes to further validate the findings of the in vivo studies and to explore the underlying mechanisms.
Here we reported that macrophage pyroptosis was activated in both fat grafts and in vitro co-culture models. DSF was found to be a potent pyroptosis inhibitor, promoting M2 macrophage polarization. In addition, DSF was demonstrated to enhance vascularization and graft retention.
Our results suggested that pyroptosis plays a crucial role in the inflammatory cascade within fat grafts. DSF, being a clinically available drug, could be translated into a clinically effective drug for improving fat graft survival by inhibiting macrophage pyroptosis, therefore inducing M2 macrophage polarization and promoting neovascularization.
移植后早期巨噬细胞介导的炎症反应限制了脂肪移植物的保留。细胞焦亡是一种广泛参与炎症性疾病的新型程序性细胞死亡方式。
本研究旨在确定脂肪移植后炎症期是否激活了巨噬细胞焦亡，并探讨焦亡抑制剂二硫化硒（DSF）在脂肪移植物保留中的效果。
我们建立了 C57BL/6 小鼠脂肪移植模型，然后分析了巨噬细胞焦亡情况。DSF（50mg/kg，每隔一天）在脂肪移植前 1 小时腹腔内注射，持续 14 天。建立了体外共培养体系，将小鼠 RAW264.7 巨噬细胞与凋亡脂肪细胞共培养，以进一步验证体内研究结果，并探讨其潜在机制。
我们报道称，巨噬细胞焦亡在脂肪移植物和体外共培养模型中均被激活。DSF 被证实是一种有效的焦亡抑制剂，可促进 M2 巨噬细胞极化。此外，DSF 还被证明可增强血管生成和移植物保留。
我们的研究结果表明，细胞焦亡在脂肪移植物的炎症级联反应中起着关键作用。DSF 作为一种临床可用的药物，通过抑制巨噬细胞焦亡来提高脂肪移植物的存活率，从而诱导 M2 巨噬细胞极化并促进血管生成，具有转化为临床有效药物的潜力。
