Claire Masterson1, James Devaney, Shahd Horie, Lisa O'Flynn, Laura Deedigan, Steve Elliman, Frank Barry, Timothy O'Brien, Daniel O'Toole, John G Laffey. 1. From the Regenerative Medicine Institute at CÚRAM Centre for Research in Medical Devices, Biomedical Sciences Building, National University of Ireland Galway, Galway, Ireland (C.M., J.D., S.H., F.B., T.O., D.O., J.G.L.) Orbsen Therapeutics Ltd., Galway, Ireland (L.O., L.D., S.E.) School of Medicine, College of Medicine, Nursing and Health Sciences, National University of Ireland, Galway, Ireland (F.B., T.O., D.O., J.G.L.) Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospitals, SAOLTA University Health Group, Galway, Ireland (T.O.) Department of Anaesthesia, Galway University Hospitals, SAOLTA University Health Group, Galway, Ireland (J.G.L.).
Abstract
WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND: : Human mesenchymal stromal cells demonstrate promise for acute respiratory distress syndrome, but current studies use highly heterogenous cell populations. We hypothesized that a syndecan 2 (CD362)-expressing human mesenchymal stromal cell subpopulation would attenuate Escherichia coli-induced lung injury and enhance resolution after ventilator-induced lung injury. METHODS: In vitro studies determined whether CD362 human mesenchymal stromal cells could modulate pulmonary epithelial inflammation, wound healing, and macrophage phagocytosis. Two in vivo rodent studies determined whether CD362 human mesenchymal stromal cells attenuated Escherichia coli-induced lung injury (n = 10/group) and enhanced resolution of ventilation-induced injury (n = 10/group). RESULTS: CD362 human mesenchymal stromal cells attenuated cytokine-induced epithelial nuclear factor kappa B activation, increased epithelial wound closure, and increased macrophage phagocytosis in vitro. CD362 human mesenchymal stromal cells attenuated Escherichia coli-induced injury in rodents, improving arterial oxygenation (mean ± SD, 83 ± 9 vs. 60 ± 8 mmHg, P < 0.05), improving lung compliance (mean ± SD: 0.66 ± 0.08 vs. 0.53 ± 0.09 ml · cm H2O, P < 0.05), reducing bacterial load (median [interquartile range], 1,895 [100-3,300] vs. 8,195 [4,260-8,690] colony-forming units, P < 0.05), and decreasing structural injury compared with vehicle. CD362 human mesenchymal stromal cells were more effective than CD362 human mesenchymal stromal cells and comparable to heterogenous human mesenchymal stromal cells. CD362 human mesenchymal stromal cells enhanced resolution after ventilator-induced lung injury in rodents, restoring arterial oxygenation (mean ± SD: 113 ± 11 vs. 89 ± 11 mmHg, P < 0.05) and lung static compliance (mean ± SD: 0.74 ± 0.07 vs. 0.45 ± 0.07 ml · cm H2O, P < 0.05), resolving lung inflammation, and restoring histologic structure compared with vehicle. CD362 human mesenchymal stromal cells efficacy was at least comparable to heterogenous human mesenchymal stromal cells. CONCLUSIONS: A CD362 human mesenchymal stromal cell population decreased Escherichia coli-induced pneumonia severity and enhanced recovery after ventilator-induced lung injury.
WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND: : Human mesenchymal stromal cells demonstrate promise for acute respiratory distress syndrome, but current studies use highly heterogenous cell populations. We hypothesized that a syndecan 2 (CD362)-expressing human mesenchymal stromal cell subpopulation would attenuate Escherichia coli-induced lung injury and enhance resolution after ventilator-induced lung injury. METHODS: In vitro studies determined whether CD362human mesenchymal stromal cells could modulate pulmonary epithelial inflammation, wound healing, and macrophage phagocytosis. Two in vivo rodent studies determined whether CD362human mesenchymal stromal cells attenuated Escherichia coli-induced lung injury (n = 10/group) and enhanced resolution of ventilation-induced injury (n = 10/group). RESULTS:CD362human mesenchymal stromal cells attenuated cytokine-induced epithelial nuclear factor kappa B activation, increased epithelial wound closure, and increased macrophage phagocytosis in vitro. CD362human mesenchymal stromal cells attenuated Escherichia coli-induced injury in rodents, improving arterial oxygenation (mean ± SD, 83 ± 9 vs. 60 ± 8 mmHg, P < 0.05), improving lung compliance (mean ± SD: 0.66 ± 0.08 vs. 0.53 ± 0.09 ml · cm H2O, P < 0.05), reducing bacterial load (median [interquartile range], 1,895 [100-3,300] vs. 8,195 [4,260-8,690] colony-forming units, P < 0.05), and decreasing structural injury compared with vehicle. CD362human mesenchymal stromal cells were more effective than CD362human mesenchymal stromal cells and comparable to heterogenous human mesenchymal stromal cells. CD362human mesenchymal stromal cells enhanced resolution after ventilator-induced lung injury in rodents, restoring arterial oxygenation (mean ± SD: 113 ± 11 vs. 89 ± 11 mmHg, P < 0.05) and lung static compliance (mean ± SD: 0.74 ± 0.07 vs. 0.45 ± 0.07 ml · cm H2O, P < 0.05), resolving lung inflammation, and restoring histologic structure compared with vehicle. CD362human mesenchymal stromal cells efficacy was at least comparable to heterogenous human mesenchymal stromal cells. CONCLUSIONS: A CD362human mesenchymal stromal cell population decreased Escherichia coli-induced pneumonia severity and enhanced recovery after ventilator-induced lung injury.
Authors: Sing Wan Wong; Stephen Lenzini; Regina Giovanni; Katherine Knowles; Jae-Won Shin Journal: Acta Biomater Date: 2021-08-05 Impact factor: 10.633
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