BACKGROUND Ischemia-reperfusion injury (IRI) plays a crucial role in the development of primary graft dysfunction (PGD) following lung transplantation. A promising novel approach to optimize donor organs before transplantation and reduce the incidence of PGD is mitochondrial transplantation. METHODS In this study, we explored the delivery of isolated mitochondria in 4 hours ex vivo lung perfusion (EVLP) before transplantation as a means to mitigate IRI. To provide a fresh and viable source of mitochondria, as well as to streamline the workflow without the need for donor muscle biopsies, we investigated the impact of autologous, allogeneic, and xenogeneic mitochondrial transplantation. In the xenogeneic settings, isolated mitochondria from mouse liver were utilized while autologous and allogeneic sources came from pig skeletal muscle biopsies. RESULTS Treatment with mitochondrial transplantation increased the P/F ratio and reduced pulmonary peak pressure of the lungs during EVLP, compared to lungs without any mitochondrial transplantation, indicating IRI mitigation. Extensive investigations using advanced light and scanning electron microscopy did not reveal evidence of acute rejection in any of the groups, indicating safe xenotransplantation of mitochondria. CONCLUSIONS Future work is needed to further explore this novel therapy for combating IRI in lung transplantation, where xenotransplantation of mitochondria may serve as a fresh, viable source to reduce IRI.

中文翻译：

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线粒体异种移植：一种减轻离体肺灌注期间缺血再灌注损伤的新策略。


背景缺血再灌注损伤 （IRI） 在肺移植后原发性移植物功能障碍 （PGD） 的发展中起着至关重要的作用。线粒体移植是一种在移植前优化供体器官并降低 PGD 发病率的有前途的新方法是线粒体移植。方法 在这项研究中，我们探讨了移植前 4 小时离体肺灌注 （EVLP） 中分离的线粒体的递送，作为减轻 IRI 的一种手段。为了提供新鲜且可行的线粒体来源，并在不需要供体肌肉活检的情况下简化工作流程，我们研究了自体、同种异体和异种线粒体移植的影响。在异种环境中，利用来自小鼠肝脏的分离线粒体，而自体和同种异体来源来自猪骨骼肌活检。结果 与没有任何线粒体移植的肺相比，线粒体移植治疗增加了 EVLP 期间的 P/F 比值并降低了肺峰值压，表明 IRI 缓解。使用先进的光学和扫描电子显微镜进行的广泛调查没有发现任何组急性排斥反应的证据，表明线粒体的异种移植是安全的。结论需要未来的工作来进一步探索这种在肺移植中对抗 IRI 的新疗法，其中线粒体的异种移植可以作为减少 IRI 的新鲜、可行的来源。