American journal of respiratory cell and molecular biology
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Am. J. Respir. Cell Mol. Biol. · May 2020
Mesenchymal Stem Cell Extracellular Vesicles Reverse Sugen/Hypoxia Pulmonary Hypertension in Rats.
Mesenchymal stem cell extracellular vesicles attenuate pulmonary hypertension, but their ability to reverse established disease in larger animal models and the duration and mechanism(s) of their effect are unknown. We sought to determine the efficacy and mechanism of mesenchymal stem cells' extracellular vesicles in attenuating pulmonary hypertension in rats with Sugen/hypoxia-induced pulmonary hypertension. Male rats were treated with mesenchymal stem cell extracellular vesicles or an equal volume of saline vehicle by tail vein injection before or after subcutaneous injection of Sugen 5416 and exposure to 3 weeks of hypoxia. ⋯ Mesenchymal stem cell extracellular vesicles injected before or after induction of pulmonary hypertension normalized right ventricular pressure and reduced right ventricular hypertrophy and muscularization of peripheral pulmonary vessels. The effect was consistent over a range of doses and dosing intervals and was associated with lower numbers of lung macrophages, a higher ratio of alternatively to classically activated macrophages (M2/M1 = 2.00 ± 0.14 vs. 1.09 ± 0.11; P < 0.01), and increased numbers of peripheral blood vessels (11.8 ± 0.66 vs. 6.9 ± 0.57 vessels per field; P < 0.001). Mesenchymal stem cell extracellular vesicles are effective at preventing and reversing pulmonary hypertension in Sugen/hypoxia pulmonary hypertension and may offer a new approach for the treatment of pulmonary arterial hypertension.
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Am. J. Respir. Cell Mol. Biol. · May 2020
FGFR2 Is Required for AEC2 Homeostasis and Survival after Bleomycin-induced Lung Injury.
Alveolar epithelial cell (AEC) injury is central to the pathogenesis of pulmonary fibrosis. Epithelial FGF (fibroblast growth factor) signaling is essential for recovery from hyperoxia- and influenza-induced lung injury, and treatment with FGFs is protective in experimental lung injury. The cell types involved in the protective effect of FGFs are not known. ⋯ In conclusion, AEC2-specific FGFR2 is critical for survival in response to bleomycin-induced lung injury. These data also suggest that a population of SPC+ AEC2s require FGFR2 signaling for maintenance in the adult lung. Preventing epithelial FGFR inhibition and/or activating FGFRs in alveolar epithelium may therefore represent a novel approach to treating lung injury and reducing fibrosis.