Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Tissue Regeneration Therapeutics Inc, Toronto, Ontario, Canada.
J Heart Lung Transplant. 2019 Nov;38(11):1214-1223. doi: 10.1016/j.healun.2019.07.006. Epub 2019 Jul 26.
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.
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 × 10 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.
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.
The administration of MSCs ameliorated ischemic injury in donor lungs during EVLP and attenuated the subsequent ischemia-reperfusion injury after transplantation.
间质基质细胞（MSC）为基础的治疗方法在体外肺灌注（EVLP）中的应用可在移植前修复受损的供体肺。本研究的目的是使用猪肺移植模型确定 EVLP 期间 MSC 治疗对缺血再灌注损伤的疗效。
在冷保存 24 小时后，猪肺随机分为 2 组（每组 n=6），对照组无 MSC 与 MSC 组，EVLP 期间通过肺动脉给予 5×10 个细胞/kg MSC。EVLP 12 小时后，进行 1 小时的第二次冷保存期，然后将左肺移植并再灌注 4 小时。
与对照组相比，MSC 组 EVLP 灌洗液中肝细胞生长因子（HGF）水平在 12 小时时显著升高，并与 MSC 组细胞死亡标志物、裂解 caspase-3 和末端脱氧核苷酸转移酶 dUTP 缺口末端标记阳性细胞显著减少相关。在 EVLP 12 小时时，MSC 组肺组织中白细胞介素（IL）-18 和干扰素γ水平明显降低，IL-4 水平明显升高，与对照组相比。移植后，MSC 组肺组织 HGF 水平较对照组明显升高，肺组织湿重/干重比明显降低。与对照组相比，MSC 组肺组织肿瘤坏死因子-α水平和病理急性肺损伤评分明显降低。
在 EVLP 期间给予 MSC 可改善供体肺的缺血性损伤，并减轻移植后随后的缺血再灌注损伤。
