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    Item type:Publication,
    Caffeine Prevents Hyperoxia-Induced Functional and Structural Lung Damage in Preterm Rabbits
    (2016)
    Taro Nagatomo
    ;
    ;
    Jute Richter
    ;
    Siegrid De Baere
    ;
    Jeroen Vanoirbeek
    <jats:p>&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Caffeine is a commonly used drug for apnea of prematurity. It may, however, also have a beneficial effect on bronchopulmonary dysplasia (BPD), which is the most common complication of extreme preterm birth. &lt;b&gt;&lt;i&gt;Objectives:&lt;/i&gt;&lt;/b&gt; To study the inflammatory, structural and functional effects of caffeine in an animal model of BPD. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Preterm New Zealand-Dendermonde rabbits (gestational day 28; term 31) were randomized to three groups: normoxia-placebo (N-P), hyperoxia-placebo (H-P) and hyperoxia-caffeine (H-C). Lung function was assessed on postnatal day 5, along with airway morphometry, vascular morphometry and a score observing airway inflammation. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Caffeine improved lung function by increasing lung volume [mean displaced volume N-P: 40.1 ± 6 ml/kg, H-P: 27.8 ± 8 ml/kg and H-C: 34.4 ± 7 ml/kg (p &lt; 0.05); total lung capacity: N-P: 1.17 ± 0.1 ml, H-P: 0.67 ± 0.1 ml and H-C: 1.1 ± 0.1 ml (p &lt; 0.05)], decreasing tissue damping [N-P: 2.7 ± 0.3 cm H&lt;sub&gt;2&lt;/sub&gt;O/ml, H-P: 4.6 ± 0.6 cm H&lt;sub&gt;2&lt;/sub&gt;O/ml and H-C: 3.2 ± 0.4 cm H&lt;sub&gt;2&lt;/sub&gt;O/ml (p &lt; 0.05)], elastance [N-P: 9.3 ± 2.4 cm H&lt;sub&gt;2&lt;/sub&gt;O/ml, H-P: 19.2 ± 7.4 cm H&lt;sub&gt;2&lt;/sub&gt;O/ml and H-C: 10.7 ± 2 cm H&lt;sub&gt;2&lt;/sub&gt;O/ml (p &lt; 0.05)] and compliance [N-P: 0.06 ± 0.01 cm H&lt;sub&gt;2&lt;/sub&gt;O/ml, H-P: 0.054 ± 0.01 cm H&lt;sub&gt;2&lt;/sub&gt;O/ml and H-C: 0.07 ± 0.013 cm H&lt;sub&gt;2&lt;/sub&gt;O/ml (p &lt; 0.05)]. Caffeine also improved histology by decreasing alveolar size [linear intercepts; N-P: 83.6 ± 1.7, H-P: 82.9 ± 1.6 and H-C: 67.3 ± 1.4 (p &lt; 0.05)], increasing radial alveolar count (N-P: 6.6 ± 0.5, H-P: 5.7 ± 0.6 and H-C: 7.05 ± 0.5) and decreasing the acute inflammation score [N-P: 0.3 ± 0.1, H-P: 0.5 ± 0.1 and H-C: 0.4 ± 0.1 (p &lt; 0.05)]. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; In preterm rabbits, caffeine reduces the functional, architectural and inflammatory pulmonary changes induced by hyperoxia in the lung.</jats:p>
      6Scopus© Citations 50
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      19Scopus© Citations 36
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    Item type:Publication,
    Upregulation of Vascular Endothelial Growth Factor in Amniotic Fluid Stem Cells Enhances Their Potential to Attenuate Lung Injury in a Preterm Rabbit Model of Bronchopulmonary Dysplasia
    (2018) ;
    Flore Lesage
    ;
    Jute Richter
    ;
    Taro Nagatomo
    ;
    Thomas Salaets
    <jats:p>&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Bronchopulmonary dysplasia (BPD) is a chronic lung disease that affects extremely preterm infants and remains – despite improvements in neonatal intensive care – a major cause of neonatal mortality and morbidity. Cell-therapeutic strategies employing mesenchymal stem cells (MSC) have been shown to modulate lung development in BPD models. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; Herein, we evaluate the potential of human amniotic fluid (hAF)-SC and hAF-SC with upregulated expression of vascular endothelial growth factor (VEGF) as cell-therapeutic agents for BPD. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Preterm rabbit pups were raised in normoxia (21% O&lt;sub&gt;2&lt;/sub&gt;) or hyperoxia (≥95% O&lt;sub&gt;2&lt;/sub&gt;). Hyperoxia-exposed pups randomly received an intraperitoneal injection of fibroblasts, naïve hAF-SC, or hAF-SC-VEGF on postnatal day (PN) 0. On PN7, surviving pups were tested for pulmonary (forced oscillation technique) and vascular (pulmonary artery Doppler ultrasound) function, and lungs were processed for morphometric measurements of parenchymal and vascular structure and inflammation. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Intraperitoneal injection of cells resulted in homing to the lungs. The lungs of hyperoxia-exposed animals displayed parenchymal and vascular structural and functional damage reminiscent of BPD, which was significantly improved after treatment with hAF-SC-VEGF. Treating hyperoxia-exposed animals with naïve AF-SC attenuated only the lung inflammation and the vascular structural defect. Treatment with fibroblasts, which were used as a cellular control, did not lead to any improvements. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; hAF-SC with upregulated VEGF expression display enhanced potential to prevent/reverse lung injury in preterm rabbits, whereas naïve hAF-SC only show a moderate therapeutic potential. These results point towards an added value of VEGF delivered by hAF-SC in the treatment of BPD.</jats:p>
    Scopus© Citations 19  8