title: Mesenchymal stromal cells are more effective than the MSC secretome in diminishing injury and enhancing recovery following ventilator-induced lung injury.
abstract: BACKGROUND
  The potential for mesenchymal stem cells (MSCs) to reduce the severity of experimental lung injury has been established in several pre-clinical studies. We have recently demonstrated that MSCs, and MSC-secreted factors (secretome), enhance lung repair and regeneration at 48 h following ventilation-induced lung injury (VILI). We wished to determine the potential for MSC therapy to exert beneficial effects in the early recovery phase following VILI when ongoing injury coexists with processes of repair, and to compare the efficacy of MSC therapy to the use of the secretome alone.
  
  
  METHODS
  Male Sprague-Dawley rats were anesthetized, oro-tracheally intubated, and subjected to high stretch mechanical ventilation until lung compliance had declined by 50 % of baseline. Animals were then weaned from mechanical ventilation, and anesthesia discontinued. Once awake and spontaneously ventilating, animals received an intravenous injection of either rodent MSCs (10 million/kg), MSC-conditioned medium, fibroblasts (10 million/kg), or vehicle. Thereafter, the animals were allowed to recover and the extent of lung injury/repair was determined after 4 h.
  
  
  RESULTS
  Treatment with MSCs diminished injury and enhanced recovery following VILI to a greater extent compared to MSC-conditioned medium, with fibroblasts proving ineffective. MSCs, but not their conditioned medium, attenuated indices of lung injury including oxygenation, respiratory compliance, and lung edema. Total lung water as assessed by wet:dry ratio, bronchoalveolar lavage total inflammatory cell, neutrophil counts, and alveolar IL-6 concentrations were reduced in the animals that received MSC therapy.
  
  
  CONCLUSIONS
  The immunomodulating and/or reparative effect of MSCs is evident early after VILI in this model. MSC-conditioned medium was not as effective as the cells themselves in diminishing injury and restoring lung structure and function.
authors.affiliation: Regenerative Medicine Institute, National University of Ireland, Galway, Ireland. hayesmairead@hotmail.com.|Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, Galway, Ireland. hayesmairead@hotmail.com.
authors.forename: Mairead
authors.initials: M
authors.lastname: Hayes
authors.affiliation: Department of Anesthesia, Keenan Research Centre for Biomedical Science of St Michael's Hospital, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. curleyg@smh.ca.|Department of Anesthesia, University of Toronto, Toronto, Canada. curleyg@smh.ca.
authors.forename: Gerard F
authors.initials: GF
authors.lastname: Curley
authors.affiliation: Department of Anesthesia, Keenan Research Centre for Biomedical Science of St Michael's Hospital, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. claire.mast@gmail.com.|Department of Anesthesia, University of Toronto, Toronto, Canada. claire.mast@gmail.com.
authors.forename: Claire
authors.initials: C
authors.lastname: Masterson
authors.affiliation: Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, Galway, Ireland. jamesdevaney@gmail.com.
authors.forename: James
authors.initials: J
authors.lastname: Devaney
authors.affiliation: Regenerative Medicine Institute, National University of Ireland, Galway, Ireland. daniel.otoole@nuigalway.ie.|Anaesthesia, School of Medicine, Clinical Sciences Institute, National University of Ireland, Galway, Ireland. daniel.otoole@nuigalway.ie.
authors.forename: Daniel
authors.initials: D
authors.lastname: O'Toole
authors.affiliation: Regenerative Medicine Institute, National University of Ireland, Galway, Ireland. laffeyj@smh.ca.|Department of Anesthesia, Keenan Research Centre for Biomedical Science of St Michael's Hospital, St. Michael's Hospital, 30 Bond Street, Toronto, ON, M5B 1W8, Canada. laffeyj@smh.ca.|Department of Anesthesia, University of Toronto, Toronto, Canada. laffeyj@smh.ca.
authors.forename: John G
authors.initials: JG
authors.lastname: Laffey
keywords: Acute respiratory distress syndrome; Inflammation; Mesenchymal stem/stromal cell; Repair; Ventilation-induced lung injury