BACKGROUND

The application of mesenchymal stromal cell (MSC)–based therapy during ex vivo lung perfusion (EVLP) could repair injured donor lungs before transplantation. The aim of this study was to determine the efficacy of MSC therapy performed during EVLP on ischemia-reperfusion injury using a pig lung transplant model.

METHODS

Following 24 hours of cold storage, pig lungs were randomly assigned to 2 groups (n = 6 each), the control group without MSC vs the MSC group, where 5 × 10⁶ cells/kg MSCs were delivered through the pulmonary artery during EVLP. After 12 hours of EVLP, followed by a 1-hour second cold preservation period, the left lung was transplanted and reperfused for 4 hours.

RESULTS

EVLP perfusate hepatocyte growth factor (HGF) level at 12 hours was significantly elevated in the MSC group compared with the control and was associated with a significant decrease in cell death markers, cleaved caspase-3 and terminal deoxynucleotidyl transferase dUTP nick end labeling–positive cells, in the MSC group. The MSC group showed significantly lower interleukin (IL)-18 and interferon gamma levels and a significantly higher IL-4 level in lung tissue at 12 hours of EVLP than the control group. After transplantation, the MSC group showed a significant increase in lung tissue HGF level compared with the control group, associated with a significantly reduced lung tissue wet-to-dry weight ratio. Lung tissue tumor necrosis factor-α level and pathological acute lung injury score were significantly lower in the MSC group than the control group.

CONCLUSIONS

The administration of MSCs ameliorated ischemic injury in donor lungs during EVLP and attenuated the subsequent ischemia-reperfusion injury after transplantation.

中文翻译：

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离体肺灌注期间的间充质基质细胞疗法可改善肺移植中的缺血再灌注损伤。

背景

在离体肺灌注（EVLP）期间应用基于间充质基质细胞（MSC）的疗法可在移植前修复受损的供体肺。这项研究的目的是确定使用猪肺移植模型在EVLP期间进行的MSC治疗对缺血再灌注损伤的疗效。

方法

冷藏24小时后，将猪肺随机分为2组（每组n  = 6），对照组为无MSC组与MSC组，其中EVLP期间通过肺动脉递送5×10 ⁶细胞/ kg MSC。EVLP 12小时后，再进行1小时的第二个冷藏阶段，移植左肺并再灌注4小时。

结果

与对照组相比，MSC组在12小时时的EVLP灌注液肝细胞生长因子（HGF）水平显着升高，并且与细胞死亡标志物，裂解的caspase-3和末端脱氧核苷酸转移酶dUTP缺口末端标记阳性细胞的显着减少有关。 ，在MSC组中。与对照组相比，MSC组在EVLP 12小时时肺组织中的白介素（IL）-18和干扰素γ水平显着降低，而在肺组织中IL-4水平显着升高。移植后，MSC组与对照组相比，肺组织HGF水平显着增加，与肺组织干重比明显降低有关。MSC组的肺组织肿瘤坏死因子-α水平和病理性急性肺损伤评分均明显低于对照组。

结论

MSCs的使用改善了EVLP期间供体肺的缺血性损伤，并减轻了移植后随后的缺血再灌注损伤。