Hypercapnic acidosis induces mitochondrial dysfunction and impairs the ability of mesenchymal stem cells to promote distal lung epithelial repair

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

Fergie, N Todd, N McClements, L

McAuley, D O’Kane, C Krasnodembskaya, A

Permalink

Publication Type:: Journal Article
Citation:: FASEB Journal, 2019, 33 (4), pp. 5585 - 5598
Issue Date:: 2019-01-01

Closed Access

	Filename	Description	Size
	MSC and ARDS.pdf	Published Version	2.19 MB	Adobe PDF	View/Open

Copyright Clearance Process

Recently Added
In Progress
Closed Access

This item is closed access and not available.

Full metadata record

Field	Value	Language
dc.contributor.author	Fergie, N	en_US
dc.contributor.author	Todd, N	en_US
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014	en_US
dc.contributor.author	McAuley, D	en_US
dc.contributor.author	O’Kane, C	en_US
dc.contributor.author	Krasnodembskaya, A	en_US
dc.date.issued	2019-01-01	en_US
dc.identifier.citation	FASEB Journal, 2019, 33 (4), pp. 5585 - 5598	en_US
dc.identifier.issn	0892-6638	en_US
dc.identifier.uri	http://hdl.handle.net/10453/130311
dc.description.abstract	© The Author(s) 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 marrow2derived 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.	en_US
dc.relation.ispartof	FASEB Journal	en_US
dc.relation.isbasedon	10.1096/fj.201802056R	en_US
dc.subject.classification	Biochemistry & Molecular Biology	en_US
dc.title	Hypercapnic acidosis induces mitochondrial dysfunction and impairs the ability of mesenchymal stem cells to promote distal lung epithelial repair	en_US
dc.type	Journal Article
utslib.citation.volume	4	en_US
utslib.citation.volume	33	en_US
utslib.for	1102 Cardiorespiratory Medicine and Haematology	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	0606 Physiology	en_US
utslib.for	1116 Medical Physiology	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	closed_access
pubs.issue	4	en_US
pubs.publication-status	Published	en_US
pubs.volume	33	en_US

Abstract:

© The Author(s) 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 marrow2derived 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.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/130311