title: Efficacy of Mesenchymal Stromal Cell Therapy for Acute Lung Injury in Preclinical Animal Models: A Systematic Review.
abstract: The Acute Respiratory Distress Syndrome (ARDS) is a devastating clinical condition that is associated with a 30-40% risk of death, and significant long term morbidity for those who survive. Mesenchymal stromal cells (MSC) have emerged as a potential novel treatment as in pre-clinical models they have been shown to modulate inflammation (a major pathophysiological hallmark of ARDS) while enhancing bacterial clearance and reducing organ injury and death. A systematic search of MEDLINE, EMBASE, BIOSIS and Web of Science was performed to identify pre-clinical studies that examined the efficacy MSCs as compared to diseased controls for the treatment of Acute Lung Injury (ALI) (the pre-clinical correlate of human ARDS) on mortality, a clinically relevant outcome. We assessed study quality and pooled results using random effect meta-analysis. A total of 54 publications met our inclusion criteria of which 17 (21 experiments) reported mortality and were included in the meta-analysis. Treatment with MSCs, as compared to controls, significantly decreased the overall odds of death in animals with ALI (Odds Ratio 0.24, 95% Confidence Interval 0.18-0.34, I2 8%). Efficacy was maintained across different types of animal models and means of ALI induction; MSC origin, source, route of administration and preparation; and the clinical relevance of the model (timing of MSC administration, administration of fluids and or antibiotics). Reporting of standard MSC characterization for experiments that used human MSCs and risks of bias was generally poor, and although not statistically significant, a funnel plot analysis for overall mortality suggested the presence of publication bias. The results from our meta-analysis support that MSCs substantially reduce the odds of death in animal models of ALI but important reporting elements were sub optimal and limit the strength of our conclusions.
authors.affiliation: Department of Medicine (Division of Critical Care), University of Ottawa, Ottawa, Ontario, Canada.|The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Lauralyn A
authors.initials: LA
authors.lastname: McIntyre
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.|Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Moher
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Fergusson
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Sullivan
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Shirley H J
authors.initials: SH
authors.lastname: Mei
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Anesthesiology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Manoj
authors.initials: M
authors.lastname: Lalu
authors.affiliation: Department of Surgery and Critical Care Medicine, Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michaels Hospital, The University of Toronto, Toronto, Ontario, Canada.
authors.forename: John
authors.initials: J
authors.lastname: Marshall
authors.affiliation: Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, Scotland, United Kingdom.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Mcleod
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Gilly
authors.initials: G
authors.lastname: Griffin
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.|Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Grimshaw
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Université Laval, Laval, Québec City, Québec, Canada.|Population Health and Optimal Health Practice Research Unit (Trauma-Emergency-Critical Care Medicine), CHU de Québec Research Center, CHU de Québec (Hôpital de l'Enfant-Jésus), Laval, Québec City, Québec, Canada.
authors.forename: Alexis
authors.initials: A
authors.lastname: Turgeon
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.
authors.forename: Marc T
authors.initials: MT
authors.lastname: Avey
authors.affiliation: Department of Medicine (Division of Critical Care), University of Ottawa, Ottawa, Ontario, Canada.|The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Cell and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rudnicki
authors.affiliation: University of Ottawa, Ottawa, Canada.
authors.forename: Mazen
authors.initials: M
authors.lastname: Jazi
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Division of Critical Care Medicine, Université Laval, Laval, Québec City, Québec, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Fishman
authors.affiliation: The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.|Department of Cell and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Duncan J
authors.initials: DJ
authors.lastname: Stewart
mesh_terms: D055371:Acute Lung Injury / Q000628:therapy*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology; D012128:Respiratory Distress Syndrome / Q000628:therapy*; D016896:Treatment Outcome
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