Department of Surgery-Organ Donation and Transplantation, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Department of Clinical Immunology, Aarhus University Hospital, Aarhus, Denmark.
Stem Cells Dev. 2020 Oct 15;29(20):1320-1330. doi: 10.1089/scd.2020.0024. Epub 2020 Sep 2.
Pretransplant normothermic machine perfusion (NMP) of donor kidneys offers the unique opportunity to perform active interventions to an isolated renal graft before transplantation. There is increasing evidence that mesenchymal stromal cells (MSCs) could have a paracrine/endocrine regenerative effect on ischemia-reperfusion injury. The purpose of this study was to determine which cytokines are secreted by MSCs during NMP of a porcine kidney. Viable porcine kidneys and autologous whole blood were obtained from a slaughterhouse. Warm ischemia time was standardized at 20 min and subsequent hypothermic machine perfusion was performed during 2-3 h. Thereafter, kidneys were machine perfused at 37°C during 7 h. After 1 h of NMP, 0, 10 cultured human adipose tissue-derived MSCs, or 10 cultured bone marrow-derived MSCs were added ( = 5 per group). In a fourth experimental group, 7-h NMP was performed with 10 adipose tissue-derived MSCs, without a kidney in the circuit. Kidneys perfused with MSCs showed lower lactate dehydrogenase and neutrophil gelatinase-associated lipocalin levels in comparison with the control group. Also, elevated levels of human hepatocyte growth factor, interleukin (IL)-6, and IL-8 were found in the perfusate of the groups perfused with MSCs compared to the control groups. This study suggests that MSCs, in contact with an injured kidney during NMP, could lead to lower levels of injury markers and induce the release of immunomodulatory cytokines.
移植前常温机器灌注（NMP）为供体肾脏提供了在移植前对孤立肾移植物进行主动干预的独特机会。越来越多的证据表明，间充质基质细胞（MSCs）可能对缺血再灌注损伤具有旁分泌/内分泌的再生作用。本研究旨在确定 MSCs 在猪肾 NMP 过程中分泌哪些细胞因子。从屠宰场获得可行的猪肾和自体全血。将热缺血时间标准化为 20 分钟，随后进行 2-3 小时的低温机器灌注。此后，在 37°C 下对肾脏进行 7 小时的机器灌注。在 NMP 1 小时后，加入 0、10 个培养的人脂肪组织源性 MSCs 或 10 个培养的骨髓源性 MSCs（每组 = 5）。在第四个实验组中，用 10 个脂肪组织源性 MSCs 进行 7 小时的 NMP，循环中没有肾脏。与对照组相比，用 MSCs 灌注的肾脏显示出较低的乳酸脱氢酶和中性粒细胞明胶酶相关脂质运载蛋白水平。此外，与对照组相比，在 MSCs 灌注组的灌流液中发现了更高水平的人肝细胞生长因子、白细胞介素（IL）-6 和 IL-8。这项研究表明，在 NMP 过程中与受损肾脏接触的 MSCs 可能导致较低水平的损伤标志物，并诱导免疫调节细胞因子的释放。
