Abstract：
The poor availability of kidney for transplantation has led to a search for new strategies to increase the donor pool. The main option is the use of organs from extended criteria donors. We evaluated the effects of hypothermic oxygenated perfusion (HOPE) with and without extracellular vesicles (EV) derived from mesenchymal stromal cells on ischemic/reperfusion injury of marginal kidneys unsuitable for transplantation. For normothermic reperfusion (NR), we used artificial blood as a substitute for red blood cells. We evaluated the global renal ischemic dam-age score (GRS), analyzed the renal ultrastructure (RU), cytochrome c oxidase (COX) IV-1 (a mitochondrial distress marker), and caspase-3 renal expression, the tubular cell proliferation index, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) tissue levels, and effluent lactate and glucose levels. HOPE+EV kidneys had lower GRS and better RU, higher COX IV-1 expression and HGF and VEGF levels and lower caspase-3 expression than HOPE kidneys. During NR, HOPE+EV renal effluent had lower lactate release and higher glucose levels than HOPE renal effluent, suggesting that the gluconeogenesis system in HOPE+EV group was pre-served. In conclusion, EV delivery during HOPE can be considered a new organ preservation strategy for increasing the donor pool and improving transplant outcome.
摘要：
用于移植的肾脏的可用性不足导致寻找新的策略来增加供体库。主要选择是使用来自扩展标准供体的器官。我们评估了有或没有间充质基质细胞衍生的细胞外囊泡（EV）的低温氧合灌注（HOPE）对不适合移植的边缘肾脏的缺血/再灌注损伤的影响。对于常温再灌注(NR)，我们用人造血液代替了红细胞.我们评估了全球肾缺血大坝年龄评分（GRS），分析肾脏超微结构（RU），细胞色素C氧化酶（COX）IV-1（线粒体窘迫标记），和caspase-3肾表达，肾小管细胞增殖指数，肝细胞生长因子（HGF）和血管内皮生长因子（VEGF）组织水平，以及废水中的乳酸和葡萄糖水平。希望+EV肾脏有较低的GRS和更好的RU，与HOPE相比，COXIV-1表达和HGF和VEGF水平更高，caspase-3表达更低。在NR期间，HOPE+EV肾流出物比HOPE肾流出物有较低的乳酸释放和较高的葡萄糖水平,提示HOPE+EV组的糖异生系统是预先保存的。总之,HOPE期间的EV递送可以被认为是增加供体库和改善移植结果的新的器官保存策略。
