Centre for Experimental Medicine, School of Medicine, Dentistry, and Biomedical Sciences, Queen's University of Belfast, Belfast, United Kingdom.
FASEB J. 2019 Apr;33(4):5585-5598. doi: 10.1096/fj.201802056R. Epub 2019 Jan 16.
Acute respiratory distress syndrome (ARDS) is a devastating disorder characterized by diffuse inflammation and edema formation. The main management strategy, low tidal volume ventilation, can be associated with the development of hypercapnic acidosis (HCA). Mesenchymal stem cells (MSCs) are a promising therapeutic candidate currently in early-phase clinical trials. The effects of HCA on the alveolar epithelium and capillary endothelium are not well established. The therapeutic efficacy of MSCs has never been reported in HCA. In the present study, we evaluated the effects of HCA on inflammatory response and reparative potential of the primary human small airway epithelial and lung microvasculature endothelial cells as well as on the capacity of bone marrow-derived MSCs to promote wound healing in vitro. We demonstrate that HCA attenuates the inflammatory response and reparative potential of primary human small airway epithelium and capillary endothelium and induces mitochondrial dysfunction. It was found that MSCs promote lung epithelial wound repair via the transfer of functional mitochondria; however, this proreparative effect of MSCs was lost in the setting of HCA. Therefore, HCA may adversely impact recovery from ARDS at the cellular level, whereas MSCs may not be therapeutically beneficial in patients with ARDS who develop HCA.-Fergie, N., Todd, N., McClements, L., McAuley, D., O'Kane, C., Krasnodembskaya, A. Hypercapnic acidosis induces mitochondrial dysfunction and impairs the ability of mesenchymal stem cells to promote distal lung epithelial repair.
急性呼吸窘迫综合征（ARDS）是一种破坏性疾病，其特征为弥漫性炎症和水肿形成。主要的管理策略，即低潮气量通气，可能与高碳酸血症（HCA）的发展有关。间充质干细胞（MSCs）是一种有前途的治疗候选物，目前正处于临床试验的早期阶段。HCA 对肺泡上皮和毛细血管内皮的影响尚未得到充分证实。MSCs 在 HCA 中的治疗效果从未被报道过。在本研究中，我们评估了 HCA 对原代人小气道上皮和肺微血管内皮细胞的炎症反应和修复潜能的影响，以及骨髓来源的 MSCs 在体外促进伤口愈合的能力。我们证明 HCA 可减轻原代人小气道上皮和毛细血管内皮的炎症反应和修复潜能，并诱导线粒体功能障碍。研究发现，MSCs 通过转移功能线粒体促进肺上皮细胞的伤口修复；然而，在 HCA 情况下，MSCs 的这种促修复作用丧失了。因此，HCA 可能会对细胞水平的 ARDS 恢复产生不利影响，而在发生 HCA 的 ARDS 患者中，MSCs 可能没有治疗益处。-Fergie, N., Todd, N., McClements, L., McAuley, D., O'Kane, C., Krasnodembskaya, A. 高碳酸血症诱导线粒体功能障碍，并损害间充质干细胞促进远端肺上皮修复的能力。
