Donation after circulatory death (DCD) can expand the donor pool effectively. A gap remains in outcome between DCD livers and living donor livers, warranting improved DCD liver quality and urgent resolution. Bone marrow mesenchymal stem cells (BMMSCs) can regulate immunity, participate in the anti-inflammatory response, and secrete cytokines. We investigated the effect of BMMSCs combined with normothermic machine perfusion (NMP) on DCD liver quality, and the role of microcirculation therein. Rat thoracic aortas were clipped to obtain DCD livers, and a rat NMP system was established. The DCD livers were grouped by preservation method: normal, static cold storage (SCS), NMP (P), and BMMSCs plus NMP (BP); storage time was up to 8 h. Liver function in outflow perfusate was detected by biochemical methods; liver tissue histopathology was observed by hematoxylin–eosin staining; hepatocyte ultrastructure was observed by transmission electron microscopy; hepatocyte apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling; liver microcirculation–related indicators were detected by immunofluorescence, immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay. Compared with SCS, P and BP significantly improved liver function and liver histological damage, reduced hepatocyte apoptosis, and repaired hepatocyte mitochondrial damage after 6 h in vitro. BP also significantly inhibited intrahepatic macrophage activation and intercellular adhesion, improved endothelial damage, and significantly improved endothelin 1–nitric oxide balance and microcirculation perfusion. In conclusion, BP can improve DCD liver microcirculation and quality. The mechanism may be the improvement of improve hepatic sinusoidal endothelial injury and microcirculation perfusion by inhibiting macrophage activation and intercellular adhesion.

中文翻译：

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骨髓间充质干细胞联合常温机器灌注改善大鼠供肝质量——肝脏微循环在循环死亡后供肝中的重要作用

循环死亡后捐赠（DCD）可以有效地扩大供体库。DCD 肝脏和活体供肝之间的结果仍然存在差距，需要改善 DCD 肝脏质量和紧急解决方案。骨髓间充质干细胞（BMMSCs）可以调节免疫、参与抗炎反应和分泌细胞因子。我们研究了 BMMSCs 结合常温机器灌注 (NMP) 对 DCD 肝脏质量的影响，以及微循环在其中的作用。剪取大鼠胸主动脉获得DCD肝脏，建立大鼠NMP系统。DCD肝脏按保存方法分组：正常、静态冷藏（SCS）、NMP（P）和BMMSCs加NMP（BP）；储存时间长达8小时。生化法检测流出液中肝功能；肝组织病理学通过苏木精-伊红染色观察；透射电镜观察肝细胞超微结构；末端脱氧核苷酸转移酶dUTP缺口末端标记检测肝细胞凋亡；通过免疫荧光、免疫组织化学、Western印迹和酶联免疫吸附试验检测肝脏微循环相关指标。与SCS相比，P和BP在体外6小时后显着改善肝功能和肝脏组织学损伤，减少肝细胞凋亡，修复肝细胞线粒体损伤。BP 还显着抑制肝内巨噬细胞活化和细胞间粘附，改善内皮损伤，并显着改善内皮素 1-一氧化氮平衡和微循环灌注。综上所述，BP可以改善DCD肝脏微循环和质量。其机制可能是通过抑制巨噬细胞活化和细胞间粘附来改善肝窦内皮损伤和微循环灌注。