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Original Paper

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

Jiménez J.a,b · Lesage F.a · Richter J.a · Nagatomo T.c · Salaets T.a · Zia S.a · Mori Da Cunha M.G.a · Vanoirbeek J.d · Deprest J.A.a,e,f · Toelen J.a,g

Author affiliations

aDepartment of Development and Regeneration, Cluster Organ Systems, KU Leuven, Leuven, Belgium
bDepartment of Obstetrics and Gynecology, Clínica Alemana, Universidad del Desarrollo, Santiago, Chile
cDepartment of Pediatrics, Ehime Prefectural Central Hospital, Ehime, Japan
dCentre for Environment and Health, Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium
eResearch Department of Maternal Fetal Medicine, UCL Institute for Women’s Health (IWH), University College London, London, United Kingdom
fDepartment of Obstetrics and Gynecology, UZ (University Hospitals) Leuven, Leuven, Belgium
gDepartment of Pediatrics, UZ Leuven, Leuven, Belgium

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Neonatology 2018;113:275–285

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: January 10, 2017
Accepted: September 26, 2017
Published online: February 01, 2018
Issue release date: Published online first (Issue-in-Progress)

Number of Print Pages: 11
Number of Figures: 4
Number of Tables: 1

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: https://www.karger.com/NEO

Abstract

Background: 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. Objective: 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. Methods: Preterm rabbit pups were raised in normoxia (21% O2) or hyperoxia (≥95% O2). 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. Results: 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. Conclusion: 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.

© 2018 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: January 10, 2017
Accepted: September 26, 2017
Published online: February 01, 2018
Issue release date: Published online first (Issue-in-Progress)

Number of Print Pages: 11
Number of Figures: 4
Number of Tables: 1

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: https://www.karger.com/NEO


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