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, 10⁷ cultured human adipose tissue-derived MSCs, or 10⁷ cultured bone marrow-derived MSCs were added (n = 5 per group). In a fourth experimental group, 7-h NMP was performed with 10⁷ 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.

中文翻译：

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在体外常温机器灌注期间用人骨髓和脂肪组织来源的间充质基质细胞治疗缺血损伤的猪肾脏。

供体肾脏的移植前常温机器灌注 (NMP) 为在移植前对孤立的肾移植物进行积极干预提供了独特的机会。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/内分泌再生作用。本研究的目的是确定在猪肾的 NMP 过程中，MSCs 分泌哪些细胞因子。活猪肾和自体全血来自屠宰场。热缺血时间标准化为 20 分钟，随后在 2-3 小时内进行低温机器灌注。此后，肾脏在 7 小时内在 37°C 下进行机器灌注。NMP 1 小时后，0, 10 ⁷培养的人脂肪组织来源的 MSC，或 10 ⁷添加培养的骨髓来源的 MSC（ 每组n = 5）。在第四个实验组中，7-h NMP 是用 10 ⁷脂肪组织来源的 MSCs 进行的，回路中没有肾脏。与对照组相比，灌注 MSC 的肾脏显示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，在用 MSC 灌注的组的灌注液中发现人肝细胞生长因子、白细胞介素 (IL)-6 和 IL-8 的水平升高。该研究表明，在 NMP 期间与受损肾脏接触的 MSCs 可能导致损伤标志物水平降低并诱导免疫调节细胞因子的释放。