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Mesenchymal stromal cells and the acute respiratory distress syndrome (ARDS): challenges for clinical application
  1. J E Millar1,
  2. J F Fraser2,
  3. D F McAuley3
  1. 1Department of Anaesthesia, Critical Care & Pain, University of Glasgow, Glasgow, UK
  2. 2Critical Care Research Group, The Prince Charles Hospital and The University of Queensland, Brisbane, Queensland, Australia
  3. 3Centre for Infection and Immunity, Queen's University Belfast, Belfast, UK
  1. Correspondence to Dr D F McAuley, Centre for Infection and Immunity, Queen's University Belfast, Health Sciences Building, 97 Lisburn Road, Belfast BT9 7BL, UK; d.f.mcauley{at}qub.ac.uk

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In contemporary reports, approximately 30% of patients with acute respiratory distress syndrome (ARDS) will die1 and up to 70% of survivors have persistent significant disability.2 Several interventions which limit injurious ventilation have been shown to reduce mortality, primarily: low-tidal volume ventilation,3 prone positioning,4 early neuromuscular blockade5 and possibly extracorporeal membrane oxygenation (ECMO).6 To date, no intervention targeted at the underlying pathophysiological process has been shown to be beneficial, including recent studies of β-agonists and statins.7 ,8

Given the failure of pharmacological interventions in ARDS, increasing interest has been shown in the potential of mesenchymal stromal cells (MSCs). While the complex actions of MSCs are not yet fully understood, they appear to attenuate lung injury via three broad mechanisms. First, they have an immunomodulatory ability, influencing both innate and adaptive immunity. This is achieved by the secretion of anti-inflammatory soluble factors, including interleukin 10 (IL-10), IL-1 receptor antagonist and prostaglandin E2.9 Second, MSCs directly augment the host response to sepsis. LL-37 is a peptide secreted by MSCs which has direct antimicrobial properties and has previously been shown to increase bacterial clearance in an Escherichia coli model of lung injury after the intratracheal administration of MSCs.10 Third, MSCs play an important role in the repair and regeneration of lung tissue following injury. This ability appears to be mediated by the secretion of several growth factors, including vascular endothelial growth factor and keratinocyte growth factor.9

In this edition of Thorax, Devaney et al …

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