Dataset Information

Treatment of Hyperoxia-Induced Lung Injury with Lung Mesenchymal Stem Cells in Mice.

ABSTRACT:

Objective

Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in preterm neonates and has no effective treatment. This study aimed to investigate the therapeutic effects of neonatal mouse lung resident mesenchymal stem cells (L-MSCs) on the hyperoxia-induced lung injury.

Methods

L-MSCs were separated and identified according to the MSC criterions. Hyperoxia-Induced Lung Injury (HILI) of neonatal KM mice was induced with hyperoxia (FiO₂?=?60%) and investigated with pathological methods. Neonatal KM mice were divided into 3 groups (hyperoxia?+?L-MSC group, hyperoxia?+?PBS group, and air control group). Mice in the hyperoxia?+?L-MSC group were treated with L-MSCs at 3, 7, and 14 days after birth. After hyperoxia exposure for 21 days, the lung pathology, Radial Alveolar Count (RAC), CD31 expression, and vascular endothelial growth factor (VEGF) expression were investigated.

Results

After hyperoxia exposure, the body weight, RAC, CD31 expression, and VEGF expression in the hyperoxia?+?L-MSC group were significantly better than those in the hyperoxia?+?PBS group but inferior to those in the air control group significantly. These indicate L-MSCs are partially protective on the lung injury of mice with hyperoxia-induced BPD.

Conclusion

L-MSCs are helpful for the prevention and treatment of BPD, and endogenous L-MSCs may play a role in the postinjury repair of the lung.

SUBMITTER: Mei Y

PROVIDER: S-EPMC6178508 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Publications

Treatment of Hyperoxia-Induced Lung Injury with Lung Mesenchymal Stem Cells in Mice.

Mei Yabo Y Chen Chong C Dong Hui H Zhang Wanqiao W Wang Yan Y Chi Ming M Feng Zhichun Z

Stem cells international 20180926

<h4>Objective</h4>Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in preterm neonates and has no effective treatment. This study aimed to investigate the therapeutic effects of neonatal mouse lung resident mesenchymal stem cells (L-MSCs) on the hyperoxia-induced lung injury.<h4>Methods</h4>L-MSCs were separated and identified according to the MSC criterions. Hyperoxia-Induced Lung Injury (HILI) of neonatal KM mice was induced with hyperoxia (FiO<sub>2</sub> = 60%) and investiga ...[more]

PMID: 30356447

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Project description:The pathophysiology of the acute lung injury (ALI) is characterized by the damage of alveolar epithelial cells, which can be repaired by exogenous bone marrow-derived mesenchymal stem cells (BMSCs). However, the migration and differentiation abilities of BMSCs are not sufficient for the purpose, and a new approach that could strengthen the repair effects of BMSCs in ALI still needs to be clarified. We have previously proved that in vitro large tumor suppressor kinase 2- (Lats2-) underexpressing BMSCs may enhance their tissue repair effects in ALI; thus, in the present study, we tried to explore whether Lats2-underexpressing BMSCs could rescue lipopolysaccharide- (LPS-) induced ALI in vivo. BMSCs from C57BL/6 mice transfected with Lats2-interfering lentivirus vector or lentivirus blank controls were transplanted intratracheally into LPS-induced ALI mice. The retention and differentiation of BMSCs in the lung were evaluated by in vivo imaging, immunofluorescence staining, and Western blotting. The lung edema and permeability were assessed by lung wet weight/body weight ratio (LWW/BW) and measurements of proteins in bronchoalveolar lavage fluid (BALF) using ELISA. Acute lung inflammation was measured by the cytokines in the lung homogenate and BALF using RT-qPCR and ELISA, respectively. Lung injury was evaluated by HE staining and lung injury scoring. Pulmonary fibrosis was evaluated by Picrosirius red staining, immunohistochemistry for ?-SMA and TGF-?1, and hydroxyproline assay and RT-qPCR for Col1?1 and Col3?1. Lats2-mediated inhibition of the Hippo pathway increased the retention of BMSCs and their differentiation toward type II alveolar epithelial cells in the lung. Furthermore, Lats2-underexpressing BMSCs improved lung edema, permeability of the lung epithelium, and lung inflammation. Finally, Lats2-underexpressing BMSCs alleviated lung injury and early pulmonary fibrosis. Our studies suggest that underexpression of Lats2 could further enhance the repair effects of BMSCs against epithelial impair and the therapeutic potential of BMSCs in ALI mice.

Project description:BackgroundThe acute respiratory distress syndrome (ARDS), a clinical complication of severe acute lung injury (ALI) in humans, is a leading cause of morbidity and mortality in critically ill patients. ALI is characterized by disruption of the lung alveolar-capillary membrane barrier and resultant pulmonary edema associated with a proteinaceous alveolar exudate. Current specific treatment strategies for ALI/ARDS are lacking. We hypothesized that mesenchymal stem cells (MSCs), with or without transfection with the vasculoprotective gene angiopoietin 1 (ANGPT1) would have beneficial effects in experimental ALI in mice.Methods and findingsSyngeneic MSCs with or without transfection with plasmid containing the human ANGPT1 gene (pANGPT1) were delivered through the right jugular vein of mice 30 min after intratracheal instillation of lipopolysaccharide (LPS) to induce lung injury. Administration of MSCs significantly reduced LPS-induced pulmonary inflammation, as reflected by reductions in total cell and neutrophil counts in bronchoalveolar lavage (BAL) fluid (53%, 95% confidence interval [CI] 7%-101%; and 60%, CI 4%-116%, respectively) as well as reducing levels of proinflammatory cytokines in both BAL fluid and lung parenchymal homogenates. Furthermore, administration of MSCs transfected with pANGPT1 resulted in nearly complete reversal of LPS-induced increases in lung permeability as assessed by reductions in IgM and albumin levels in BAL (96%, CI 6%-185%; and 74%, CI 23%-126%, respectively). Fluorescently tagged MSCs were detected in the lung tissues by confocal microscopy and flow cytometry in both naïve and LPS-injured animals up to 3 d.ConclusionsTreatment with MSCs alone significantly reduced LPS-induced acute pulmonary inflammation in mice, while administration of pANGPT1-transfected MSCs resulted in a further improvement in both alveolar inflammation and permeability. These results suggest a potential role for cell-based ANGPT1 gene therapy to treat clinical ALI/ARDS.

Dataset Information

Treatment of Hyperoxia-Induced Lung Injury with Lung Mesenchymal Stem Cells in Mice.

Objective

Methods

Results

Conclusion

Publications

Treatment of Hyperoxia-Induced Lung Injury with Lung Mesenchymal Stem Cells in Mice.

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