Mesenchymal stem cells enhance recovery and repair following ventilator-induced lung injury in the rat
- Gerard F Curley1,2,
- Mairead Hayes1,2,
- Bilal Ansari1,2,
- Georgina Shaw3,
- Aideen Ryan3,
- Frank Barry3,
- Timothy O'Brien3,
- Daniel O'Toole2,3,
- John G Laffey1,2,3
- 1Department of Anaesthesia, School of Medicine, Clinical Sciences Institute, Galway, Ireland
- 2Lung Biology Group, National Centre for Biomedical Engineering Sciences, Galway, Ireland
- 3Regenerative Medicine Institute, National University of Ireland, Galway, Ireland
- Correspondence to Professor John G Laffey, Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, Galway, Ireland;
Contributors JGL, GFC, TO'B, DOT and FB designed the study. GFC and MH performed the experiments. BA carried out the cytokine assays. GFC, AR and GS harvested and characterised the mesenchymal stem cells. JGL analysed the data. GFC, DOT and JGL drafted the manuscript and are guarantors of the paper.
- Received 6 September 2011
- Accepted 27 October 2011
- Published Online First 21 November 2011
Background Bone-marrow derived mesenchymal stem cells (MSCs) reduce the severity of evolving acute lung injury (ALI), but their ability to repair the injured lung is not clear. A study was undertaken to determine the potential for MSCs to enhance repair after ventilator-induced lung injury (VILI) and elucidate the mechanisms underlying these effects.
Methods Anaesthetised rats underwent injurious ventilation which produced severe ALI. Following recovery, they were given an intravenous injection of MSCs (2×106 cells) or vehicle immediately and a second dose 24 h later. The extent of recovery following VILI was assessed after 48 h. Subsequent experiments examined the potential for non-stem cells and for the MSC secretome to enhance VILI repair. The contribution of specific MSC-secreted mediators was then examined in a wound healing model.
Results MSC therapy enhanced repair following VILI. MSCs enhanced restoration of systemic oxygenation and lung compliance, reduced total lung water, decreased lung inflammation and histological lung injury and restored lung structure. They attenuated alveolar tumour necrosis factor α concentrations while increasing concentrations of interleukin 10. These effects were not seen with non-stem cells (ie, rat fibroblasts). MSC-secreted products also enhanced lung repair and attenuated the inflammatory response following VILI. The beneficial effect of the MSC secretome on repair of pulmonary epithelial wounds was attenuated by prior depletion of keratinocyte growth factor.
Conclusion MSC therapy enhances lung repair following VILI via a paracrine mechanism that may be keratinocyte growth factor-dependent.
- Acute respiratory distress syndrome
- ventilation induced lung injury
- mesenchymal stem cell
- airway epithelium
- assisted ventilation
- bacterial infection
- non invasive ventilation
- systemic disease and lungs
- viral infection
- cytokine biology
See Editorial, p 475
Data from this paper were presented at the American Thoracic Society Annual Scientific Meeting, Denver, Colorado, May 2011.
Funding The European Research Council (grant number ERC-2007-StG 207777) and Health Research Board, Dublin, Ireland (grant number RP/2008/193) provided unrestricted funds for these studies. Dr Curley was supported by a fellowship from Molecular Medicine Ireland (HEA PRTLI Cycle A).
Competing interests None.
Patient consent Not needed.
Provenance and peer review Not commissioned; externally peer reviewed.