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Author: search.filters.author.Thomas SalaetsSubject: search.filters.subject.preterm birth

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    Preterm birth impairs postnatal lung development in the neonatal rabbit model
    (2020)
    Thomas Salaets
    ;
    Margo Aertgeerts
    ;
    André Gie
    ;
    Janne Vignero
    ;
    Derek de Winter
    <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>Bronchopulmonary dysplasia continues to cause important respiratory morbidity throughout life, and new therapies are needed. The common denominator of all BPD cases is preterm birth, however most preclinical research in this area focusses on the effect of hyperoxia or mechanical ventilation. In this study we investigated if and how prematurity affects lung structure and function in neonatal rabbits.</jats:p> </jats:sec><jats:sec> <jats:title>Methods</jats:title> <jats:p>Pups were delivered on either day 28 or day 31. For each gestational age a group of pups was harvested immediately after birth for lung morphometry and surfactant protein B and C quantification. All other pups were hand raised and harvested on day 4 for the term pups and day 7 for the preterm pups (same corrected age) for lung morphometry, lung function testing and qPCR. A subset of pups underwent microCT and dark field imaging on day 0, 2 and 4 for terms and on day 0, 3, 5 and 7 for preterms.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Preterm pups assessed at birth depicted a more rudimentary lung structure (larger alveoli and thicker septations) and a lower expression of surfactant proteins in comparison to term pups. MicroCT and dark field imaging revealed delayed lung aeration in preterm pups, in comparison to term pups. Preterm birth led to smaller pups, with smaller lungs with a lower alveolar surface area on day 7/day 4. Furthermore, preterm birth affected lung function with increased tissue damping, tissue elastance and resistance and decreased dynamic compliance. Expression of vascular endothelial growth factor (VEGFA) was significantly decreased in preterm pups, however in the absence of structural vascular differences.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Preterm birth affects lung structure and function at birth, but also has persistent effects on the developing lung. This supports the use of a preterm animal model, such as the preterm rabbit, for preclinical research on BPD. Future research that focuses on the identification of pathways that are involved in in-utero lung development and disrupted by pre-term birth, could lead to novel therapeutic strategies for BPD.</jats:p> </jats:sec>
    Scopus© Citations 23  1
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    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)
    JIMENEZ GREZ, JULIO ALBERTO  
    ;
    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