Hypercapnic acidosis induces mitochondrial dysfunction and impairs the ability of mesenchymal stem cells to promote distal lung epithelial repair. Issue 4 (16th January 2019)

• Record Type: Journal Article
• Authors: Fergie, Nicola; Todd, Naomi; McClements, Lana; McAuley, Danny; O'Kane, Cecilia; Krasnodembskaya, Anna
• Is Part Of: FASEB journal. Volume 33:Issue 4(2019)
• Page Start: 5585
• Page End: 5598
• Publication Date: 2019-01-16
• Subjects: ARDS -- hypercapnic acidosis -- mitochondrial transfer -- wound healing; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201802056R
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: 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. FASEB J. 33, 5585–5598 (2019). www.fasebj.org