TY -的T1 - MSC细胞外囊泡救援线粒体功能障碍和改善ARDS的临床相关模型的屏障完整性JF -欧洲呼吸杂志》乔和J - 10.1183/13993003.02978 -2020欧元SP - 2002978 AU -席尔瓦,Johnatas南美洲盟——苏、粤盟——Calfee卡罗琳S AU -卢基,凯文•L AU -维斯丹尼·f·丹尼尔·AU - McAuley AU - O 'Kane,塞西莉亚AU - Krasnodembskaya,安娜·d·Y1 - 2020/01/01 UR - //www.qdcxjkg.com/content/early/2020/11/26/13993003.02978 - 2020. -抽象N2 -肺泡epithelial-capillary屏障的破坏是一个急性呼吸窘迫综合征(ARDS)的标志。ARDS中线粒体功能障碍对肺泡-毛细血管屏障损害的作用尚不清楚。间充质间质细胞源性细胞外囊泡(MSC EVs)被认为是一种无细胞治疗ARDS的方法。线粒体转移对MSCs和MSC ev的治疗效果非常重要。在这里，我们研究了线粒体功能障碍对ARDS患者肺泡上皮和内皮屏障损伤的贡献，以及MSC ev通过线粒体转移调节肺泡-毛细血管屏障完整性的能力。采用急性呼吸窘迫综合征(ARDS)患者的血浆或内毒素刺激人小气道上皮细胞和肺微血管内皮细胞及人精确切肺切片(PCLSs)，并给予MSC ev治疗，评估其屏障特性和线粒体功能。用MSC ev处理lps损伤小鼠，观察肺损伤程度和肺组织线粒体呼吸。炎症刺激导致渗透性增加，并伴有原代细胞和pcls中明显的线粒体功能障碍。来源于正常间充质干细胞的EV能恢复屏障的完整性和正常水平的氧化磷酸化，而不含线粒体的EV制剂则无效。 In vivo, presence of mitochondria was critical for EV ability to reduce lung injury and restore mitochondrial respiration in the lung tissue.In the ARDS environment MSC-EVs improve alveolar-capillary barrier properties through restoration of mitochondrial functions at least partially via mitochondrial transfer.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Silva has nothing to disclose.Conflict of interest: Dr. Su has nothing to disclose.Conflict of interest: Dr. Calfee reports grants from NIH, during the conduct of the study; grants and personal fees from Roche/Genentech, grants and personal fees from Bayer, personal fees from Quark Pharmaceuticals, personal fees from Prometic, personal fees from Gen1e Life Sciences, personal fees from Vasomune, outside the submitted work;.Conflict of interest: Dr. Delucchi has nothing to disclose.Conflict of interest: Dr. Weiss has nothing to disclose.Conflict of interest: Outside the submitted work, Dr. McAuley reports personal fees from consultancy for GlaxoSmithKline, Boehringer Ingelheim and Bayer. In addition his institution has received funds from grants from the UK NIHR, Wellcome Trust and others. In addition, Dr. McAuley has a patent issued to his institution for a treatment for ARDS. DFM is a Director of Research for the Intensive Care Society and NIHR EME Programme Director.Conflict of interest: Dr. O'Kane reports Bayer, grants from Wellcome Trust,, MRC and NI HSC R&D, and that spouse has received consultancy fees from GlaxoSmithKline, Boehringer Ingelheim and Bayer, outside the submitted work;.Conflict of interest: Dr. Krasnodembskaya reports grants from Medical Research Council, UK, during the conduct of the study;. ER -