Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden; Department of Cardiothoracic Anesthesia and Intensive Care, Skåne University Hospital, Lund, Sweden.
Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden; Department of Clinical Sciences, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden; Department of Cardiothoracic Surgery, NYU Grossman School of Medicine, New York, New York.
J Heart Lung Transplant. 2024 Dec;43(12):2018-2030. doi: 10.1016/j.healun.2024.08.014. Epub 2024 Aug 23.
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.
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 × 10 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).
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 PaO/FiO ratios and reduced incidence of PGD.
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.
肺移植受到供体肺利用率低的阻碍。由于担心移植后原发性移植物功能障碍，感染并发症是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治疗方法。足月羊水来源的肺特异性间充质干细胞治疗可能会再生受损的肺。这些细胞以前在其他呼吸系统疾病中表现出炎症调节作用，我们假设治疗会改善供体肺的质量和术后结果。
在移植模型中，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体外肺灌注（EVLP）上。治疗包括 3 次 2×10 个细胞/kg：一次在 EVLP 期间，两次在移植后。根据临床相关参数评估供体和受体，并在评估原发性移植物功能障碍（PGD）前对受体进行 3 天的随访。
重复注射细胞治疗可降低免疫细胞计数，减轻组织学炎症迹象，并降低血浆和支气管肺泡灌洗液中的细胞因子，从而减轻炎症。接受治疗的受体显示出改善的肺功能，包括增加 PaO/FiO 比值和降低 PGD 的发生率。
在 EVLP 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有关。细胞治疗可被视为增加可用于移植的肺数量和改善术后结果的潜在治疗方法。
