猪米色脂肪生成的荟萃分析及跨物种CD137-CD137L分子对接：对猪-人异种移植的潜在意义。
完整摘要 · 中文译文
基因编辑技术的突破使猪到人的异种移植走到了临床前沿。然而，受者体内复杂的病理生理环境对移植物在微观尺度上的影响长期以来一直被学术界忽视。本研究以广泛存在于供体器官中的基质血管组分（SVF）细胞和前脂肪细胞为对象，探讨术后抗炎药物（如地塞米松）和手术应激（去甲肾上腺素）诱导米色脂肪生成的潜在机制，及其与宿主免疫系统激活的可能关系。文献检索和研究筛选的报告以PRISMA 2020为依据。检索了五个信息来源，并将九项关于实验性诱导猪脂肪组织米色化（主要是在体外）的相关研究纳入标志物特异性荟萃分析。荟萃分析显示，在实验性诱导猪米色脂肪生成过程中，CD137、CIDEA、UCP3、PGC1α和DIO2的合并表达水平较高。为了探索跨物种相互作用的结构可行性，使用AlphaFold 3对候选蛋白CD137进行了分子对接分析。预测的猪CD137-人CD137L结合能为-9.4 kcal/mol，人同源复合物的结合能为-9.0 kcal/mol。这些计算预测表明存在结构上可行的相互作用，但结果并未证明更强的生物结合、巨噬细胞激活或免疫排斥。总体而言，这些发现支持一个假说，即猪脂肪细胞米色化可能通过减弱局部免疫反应来促进异种移植物存活，并为移植物脂肪组织在异种移植中的作用提供了新的视角。 衰老与CD137相关的跨物种相互作用可能与异种移植免疫代谢相关；需要在异种移植模型中进行直接实验验证。
完整摘要 · 英文原文
Breakthroughs in gene-editing technologies have brought pig-to-human xenotransplantation to the clinical forefront. Nevertheless, the micro-scale impacts of the complex pathophysiological milieu within recipients on grafts have long been overlooked by the academic community. Focusing on stromal vascular fraction (SVF) cells and preadipocytes widely present in donor organs, this study explores the potential mechanism underlying beige adipogenesis induced by post-operative anti-inflammatory drugs (e.g., dexamethasone) and surgical stress (norepinephrine), as well as its possible relationship with host immune system activation. The literature search and study-selection reporting were informed by PRISMA 2020. Five information sources were searched, and nine relevant studies on experimentally induced porcine adipose beiging, predominantly in vitro, were included in marker-specific meta-analyses. The meta-analysis showed a higher pooled expression of CD137, CIDEA, UCP3, PGC1α and DIO2 during experimentally induced porcine beige adipogenesis. To explore the structural plausibility of cross-species interaction, molecular docking analysis of the candidate protein CD137 was performed using AlphaFold 3. The predicted binding energies were -9.4 kcal/mol for porcine CD137-human CD137L and -9.0 kcal/mol for the human homologous complex. These computational predictions suggest a structurally plausible interaction, but the results do not demonstrate stronger biological binding, macrophage activation, or immune rejection. Overall, the findings support a hypothesis that porcine adipocyte beiging and CD137-related cross-species interactions may be relevant to xenograft immunometabolism; direct experimental validation in xenotransplantation models is required.