title: Cryopreserved, Xeno-Free Human Umbilical Cord Mesenchymal Stromal Cells Reduce Lung Injury Severity and Bacterial Burden in Rodent Escherichia coli-Induced Acute Respiratory Distress Syndrome.
abstract: OBJECTIVE
  Although mesenchymal stem/stromal cells represent a promising therapeutic strategy for acute respiratory distress syndrome, clinical translation faces challenges, including scarcity of bone marrow donors, and reliance on bovine serum during mesenchymal stem/stromal cell proliferation. We wished to compare mesenchymal stem/stromal cells from human umbilical cord, grown in xeno-free conditions, with mesenchymal stem/stromal cells from human bone marrow, in a rat model of Escherichia coli pneumonia. In addition, we wished to determine the potential for umbilical cord-mesenchymal stem/stromal cells to reduce E. coli-induced oxidant injury.
  
  
  METHODS
  Randomized animal study.
  
  
  METHODS
  University research laboratory.
  
  
  METHODS
  Male Sprague-Dawley rats.
  
  
  METHODS
  Acute respiratory distress syndrome was induced in rats by intratracheal instillation of E. coli (1.5-2 × 10 CFU/kg). "Series 1" compared the effects of freshly thawed cryopreserved umbilical cord-mesenchymal stem/stromal cells with bone marrow-mesenchymal stem/stromal cells on physiologic indices of lung injury, cellular infiltration, and E. coli colony counts in bronchoalveolar lavage. "Series 2" examined the effects of cryopreserved umbilical cord-mesenchymal stem/stromal cells on survival, as well as measures of injury, inflammation and oxidant stress, including production of reactive oxidative species, reactive oxidative species scavenging by superoxide dismutase-1 and superoxide dismutase-2.
  
  
  RESULTS
  In "Series 1," animals subjected to E. coli pneumonia who received umbilical cord-mesenchymal stem/stromal cells had improvements in oxygenation, respiratory static compliance, and wet-to-dry ratios comparable to bone marrow-mesenchymal stem/stromal cell treatment. E. coli colony-forming units in bronchoalveolar lavage were reduced in both cell therapy groups, despite a reduction in bronchoalveolar lavage neutrophils. In series 2, umbilical cord-mesenchymal stem/stromal cells enhanced animal survival and decreased alveolar protein and proinflammatory cytokine concentrations, whereas increasing interleukin-10 concentrations. Umbilical cord-mesenchymal stem/stromal cell therapy decreased nicotinamide adenine dinucleotide phosphate-oxidase 2 and inducible nitric oxide synthase and enhanced lung concentrations of superoxide dismutase-2, thereby reducing lung tissue reactive oxidative species concentrations.
  
  
  CONCLUSIONS
  Our results demonstrate that freshly thawed cryopreserved xeno-free human umbilical cord-mesenchymal stem/stromal cells reduce the severity of rodent E. coli-induced acute respiratory distress syndrome. Umbilical cord-mesenchymal stem/stromal cells, therefore, represent an attractive option for future clinical trials in acute respiratory distress syndrome.
authors.affiliation: 1Departments of Anesthesia and Critical Care Medicine, St. Michael's Hospital, Toronto, ON, Canada. 2Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, ON, Canada. 3Department of Anesthesia and Interdepartmental Division of Critical Care, University of Toronto, ON, Canada. 4Department of Anaesthesia, National University of Ireland, Galway. 5Departments of Anesthesia, Physiology and Interdepartmental Division of Critical Care, University of Toronto, ON, Canada.
authors.forename: Gerard F
authors.initials: GF
authors.lastname: Curley
authors.forename: Mirjana
authors.initials: M
authors.lastname: Jerkic
authors.forename: Steve
authors.initials: S
authors.lastname: Dixon
authors.forename: Grace
authors.initials: G
authors.lastname: Hogan
authors.forename: Claire
authors.initials: C
authors.lastname: Masterson
authors.forename: Daniel
authors.initials: D
authors.lastname: O'Toole
authors.forename: James
authors.initials: J
authors.lastname: Devaney
authors.forename: John G
authors.initials: JG
authors.lastname: Laffey
mesh_terms: D000818:Animals; D016895:Culture Media, Serum-Free; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000150:complications; D006801:Humans; D055370:Lung Injury / Q000517:prevention & control*; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology; D018384:Oxidative Stress; D018410:Pneumonia, Bacterial / Q000150:complications / Q000628:therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000628:therapy*; D014470:Umbilical Cord / Q000166:cytology
chemical_list: D016895:Culture Media, Serum-Free