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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.
Curley, Gerard F; Jerkic, Mirjana; Dixon, Steve; Hogan, Grace; Masterson, Claire; O'Toole, Daniel; Devaney, James; Laffey, John G.
Afiliação
  • Curley GF; 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.
Crit Care Med ; 45(2): e202-e212, 2017 Feb.
Article em En | MEDLINE | ID: mdl-27861182
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. DESIGN: Randomized animal study. SETTING: University research laboratory. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: 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. MEASUREMENTS AND MAIN 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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome do Desconforto Respiratório / Transplante de Células-Tronco Mesenquimais / Lesão Pulmonar Idioma: En Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Síndrome do Desconforto Respiratório / Transplante de Células-Tronco Mesenquimais / Lesão Pulmonar Idioma: En Ano de publicação: 2017 Tipo de documento: Article