Hyperoxia-induced bronchopulmonary dysplasia: better models for better therapies

Abstract

Bronchopulmonary dysplasia (BPD) is a chronic lung disease caused by exposure to high levels of oxygen (hyperoxia) and is the most common complication that affects preterm newborns. At present, there is no cure for BPD. Infants can recover from BPD; however, they will suffer from significant morbidity into adulthood in the form of neurodevelopmental impairment, asthma and emphysematous changes of the lung. The development of hyperoxia-induced lung injury models in small and large animals to test potential treatments for BPD has shown some success, yet a lack of standardization in approaches and methods makes clinical translation difficult. In vitro models have also been developed to investigate the molecular pathways altered during BPD and to address the pitfalls associated with animal models. Preclinical studies have investigated the efficacy of stem cell-based therapies to improve lung morphology after damage. However, variability regarding the type of animal model and duration of hyperoxia to elicit damage exists in the literature. These models should be further developed and standardized, to cover the degree and duration of hyperoxia, type of animal model, and lung injury endpoint, to improve their translational relevance. The purpose of this Review is to highlight concerns associated with current animal models of hyperoxia-induced BPD and to show the potential of in vitro models to complement in vivo studies in the significant improvement to our understanding of BPD pathogenesis and treatment. The status of current stem cell therapies for treatment of BPD is also discussed. We offer suggestions to optimize models and therapeutic modalities for treatment of hyperoxia-induced lung damage in order to advance the standardization of procedures for clinical translation.

Using a neonatal rat model to explore the therapeutic potential of coenzyme Q10 in prematurity under hyperoxia

“…Therefore, neonatal rats are suitable for simulating the hallmark symptoms of neonatal BPD. 41,42 The results of the lung in our study are intriguing. At the 16th oxygen exposure, the lung tissue did not increase MDA or change the level of antioxidants.…”

“…Full‐term rats are born in the saccular stage of lung development, which corresponds to human lung development at 26–28 weeks of gestation. Therefore, neonatal rats are suitable for simulating the hallmark symptoms of neonatal BPD 41,42 …”

Change of intestinal microbiota in mice model of bronchopulmonary dysplasia

“…Mice, like premature infants, are in the saccular stage of lung development at birth, which can simulate the development process of lung tissue in children with BPD. Moreover, mice are very suitable to be selected as animal models because of their high gene homology with human genes, short pregnancy cycle and low test cost ( Giusto et al, 2021 ). Pregnant mice of specific-pathogen free (SPF) Kunming mice were purchased from Sipeifu Biotech (Beijing, China; Approval No.…”

“…Neonatal mice were randomly divided into control group ( n = 5 L) and BPD group ( n = 5 L), and there are 5–6 mice in each litter. There is no consensus on the optimal oxygen for inducing BPD models ( Giusto et al, 2021 ), and we referred to one of the development model of mice ( Nardiello et al, 2017 ). Neonatal mice in BPD group were subject to high concentration of oxygen (80 ± 5%) for 3 weeks.…”

Phospholipase Cβ2 Promotes Vascular Endothelial Growth Factor Induced Vascular Permeability

“…An initial increase in VEGFA in bronchoalveolar lavage (BAL) fluid followed by decreased VEGFA levels in persistent hyperoxic conditions. [47][48][49] Upon return to room air, a dramatic increase in VEGFA levels is observed. 50,51 In this study, animals were exposed to hyperoxia for 72 hours, followed by return to room air for 4 hours.…”