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

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Abstract

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−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 H2O−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.

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