Syndecan-2–positive, Bone Marrow–derived Human Mesenchymal Stromal Cells Attenuate Bacterial-induced Acute Lung Injury and Enhance Resolution of Ventilator-induced Lung Injury in Rats. (September 2018)

• Record Type: Journal Article
• Authors: Masterson, Claire; Devaney, James; Horie, Shahd; O'Flynn, Lisa; Deedigan, Laura; Elliman, Steve; Barry, Frank; O'Brien, Timothy; O'Toole, Daniel; Laffey, John G.
• Is Part Of: Anesthesiology. Volume 129:Number 3(2018)
• Publication Date: 2018-09
• Subjects: Anesthesiology -- Periodicals; Anesthetics -- Periodicals; Anesthesia -- Periodicals; 617.9605
• DOI: 10.1097/ALN.0000000000002327
• Languages: English
• ISSNs: 0003-3022

Abstract

Abstract : What We Already Know about This Topic: Human mesenchymal stromal cells diminish injury and enhance recovery and repair after ventilator-induced lung injury in animals Current methods of isolating mesenchymal stromal cells result in a heterogeneous mix of cell types, which may be suboptimal What This Article Tells Us That Is New: Pure subpopulations of bone marrow–derived human mesenchymal stromal cells were isolated on the basis of expression of the cell surface marker syndecan 2 Intravenous injection of these cells attenuated Escherichia coli –induced injury and enhanced resolution of ventilator-induced lung injury in rats, reducing lung inflammation and histologic injury and improving lung compliance and arterial oxygenation Cells expressing syndecan 2 were more effective than those not expressing syndecan 2 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 H2 O −1, 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 H2 O −1, 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. Abstract : Pure subpopulations of bone marrow–derived human mesenchymal stromal cells were isolated on the basis of expression of the cell surface marker syndecan 2. Intravenous injection of these cells attenuated Escherichia coli –induced injury and enhanced resolution of ventilator-induced lung injury in rats, reducing lung inflammation and histologic injury and improving lung compliance and arterial oxygenation. Cells expressing syndecan 2 were more effective than those not expressing syndecan 2.Supplemental Digital Content is available in the text.