Niroomand Anna, Hirdman Gabriel, Pierre Leif, Ghaidan Haider, Kjellström Sven, Stenlo Martin, Hyllén Snejana, Olm Franziska, Lindstedt Sandra
Department of Clinical Sciences, Lund University, Lund, Sweden.
Lund Stem Cell Center, Lund University, Lund, Sweden.
Front Cardiovasc Med. 2023 Oct 2;10:1274444. doi: 10.3389/fcvm.2023.1274444. eCollection 2023.
In recent years, the field of graft preservation has made considerable strides in improving outcomes related to solid organ restoration and regeneration. Ex vivo lung perfusion (EVLP) in line with the related devices and treatments has yielded promising results within preclinical and clinical studies, with the potential to improve graft quality. Its main benefit is to render marginal and declined donor lungs suitable for transplantation, ultimately increasing the donor pool available for transplantation. In addition, using such therapies in machine perfusion could also increase preservation time, facilitating logistical planning. Cytokine adsorption has been demonstrated as a potentially safe and effective therapy when applied to the EVLP circuit and post-transplantation. However, the mechanism by which this therapy improves the donor lung on a molecular basis is not yet fully understood.
We hypothesized that there were characteristic inflammatory and immunomodulatory differences between the lungs treated with and without cytokine adsorption, reflecting proteomic changes in the gene ontology pathways and across inflammation-related proteins. In this study, we investigate the molecular mechanisms and signaling pathways of how cytokine adsorption impacts lung function when used during EVLP and post-transplantation as hemoperfusion in a porcine model. Lung tissues during EVLP and post-lung transplantation were analyzed for their proteomic profiles using mass spectrometry.
We found through gene set enrichment analysis that the inflammatory and immune processes and coagulation pathways were significantly affected by the cytokine treatment after EVLP and transplantation.
In conclusion, we showed that the molecular mechanisms are using a proteomic approach behind the previously reported effects of cytokine adsorption when compared to the non-treated transplant recipients undergoing EVLP.
近年来，移植物保存领域在改善与实体器官修复和再生相关的结果方面取得了长足进展。符合相关设备和治疗方法的体外肺灌注（EVLP）在临床前和临床研究中已取得了有前景的结果，具有改善移植物质量的潜力。其主要益处是使边缘性和功能下降的供体肺适合移植，最终增加可用于移植的供体库。此外，在机器灌注中使用此类疗法还可延长保存时间，便于后勤规划。细胞因子吸附已被证明在应用于EVLP回路和移植后是一种潜在安全有效的疗法。然而，这种疗法在分子水平上改善供体肺的机制尚未完全了解。
我们假设，在进行细胞因子吸附治疗和未进行该治疗的肺之间存在特征性的炎症和免疫调节差异，这反映了基因本体途径和炎症相关蛋白中的蛋白质组变化。在本研究中，我们在猪模型中研究了细胞因子吸附在EVLP期间及移植后作为血液灌注使用时影响肺功能的分子机制和信号通路。使用质谱分析EVLP期间和肺移植后的肺组织的蛋白质组概况。
通过基因集富集分析，我们发现炎症和免疫过程以及凝血途径在EVLP和移植后的细胞因子治疗中受到显著影响。
总之，与未接受治疗的接受EVLP的移植受者相比，我们表明分子机制是采用蛋白质组学方法来研究先前报道的细胞因子吸附的作用。
