BACKGROUND Lung transplantation is hindered by low donor lung utilization rates. Infectious complications are reasons to decline donor grafts due to fear of post-transplant primary graft dysfunction. Mesenchymal stem cells are a promising therapy currently investigated in treating lung injury. Full-term amniotic fluid-derived lung-specific mesenchymal stem cell treatment may regenerate damaged lungs. These cells have previously demonstrated inflammatory mediation in other respiratory diseases, and we hypothesized that treatment would improve donor lung quality and postoperative outcomes. METHODS In a transplantation model, donor pigs were stratified to either the treated or the nontreated group. Acute respiratory distress syndrome was induced in donor pigs and harvested lungs were placed on ex vivo lung perfusion (EVLP) before transplantation. Treatment consisted of 3 doses of 2 × 106 cells/kg: one during EVLP and 2 after transplantation. Donors and recipients were assessed on clinically relevant parameters and recipients were followed for 3 days before evaluation for primary graft dysfunction (PGD). RESULTS Repeated injection of the cell treatment showed reductions in inflammation seen through lowered immune cell counts, reduced histology signs of inflammation, and decreased cytokines in the plasma and bronchoalveolar lavage fluid. Treated recipients showed improved pulmonary function, including increased PaO2/FiO2 ratios and reduced incidence of PGD. CONCLUSIONS Repeated injection of lung-specific cell treatment during EVLP and post transplant was associated with improved function of previously damaged lungs. Cell treatment may be considered as a potential therapy to increase the number of lungs available for transplantation and the improvement of postoperative outcomes.

中文翻译：

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羊水来源的间充质干细胞在猪模型中移植后可减轻炎症并改善肺功能。


背景 供体肺利用率低阻碍了肺移植。感染并发症是由于担心移植后原发性移植物功能障碍而拒绝供体移植物的原因。间充质干细胞是目前治疗肺损伤的一种有前途的疗法。足月羊水来源的肺特异性间充质干细胞治疗可以再生受损的肺。这些细胞之前在其他呼吸系统疾病中已经证明了炎症介导，我们假设治疗会改善供体肺质量和术后结果。方法 在移植模型中，将供体猪分为治疗组或未治疗组。在供体猪中诱导急性呼吸窘迫综合征，并在移植前将收获的肺置于离体肺灌注 （EVLP） 上。治疗包括 3 剂 2 × 106 个细胞/kg：1 剂在 EVLP 期间，2 剂在移植后。根据临床相关参数评估供者和受者，并在评估原发性移植物功能障碍 （PGD） 之前对受者进行 3 天的随访。结果重复注射细胞治疗显示，通过降低免疫细胞计数、减少炎症的组织学体征以及血浆和支气管肺泡灌洗液中的细胞因子减少，炎症减少。接受治疗的受者肺功能得到改善，包括 PaO2/FiO2 比值增加和 PGD 发生率降低。结论 EVLP 期间和移植后重复注射肺特异性细胞治疗与先前受损肺功能的改善相关。 细胞治疗可能被认为是一种潜在的疗法，可以增加可用于移植的肺数量和改善术后结局。