Modelling Bronchopulmonary Dysplasia in Animals: Arguments for the Preterm Rabbit Model
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Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs
Published on: October 31, 2025
Thomas Salaets1,2, Andre Gie1, Bieke Tack2
1Department of Development and Regeneration, Cluster Organ Systems, Faculty of Medicine, University of Leuven, Herestraat 49, Leuven 3000, Belgium.
Insights
Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. This review discusses animal models that mimic human BPD, aiding in the development of new treatments.
Area of Science:
- Neonatology
- Pulmonology
- Comparative Medicine
Background:
- Bronchopulmonary dysplasia (BPD) is a significant cause of morbidity in premature infants, despite advances in neonatal care.
- Improving outcomes for BPD necessitates the investigation of novel therapeutic and preventive strategies.
- Animal models are crucial for studying BPD pathophysiology and evaluating potential interventions.
Purpose of the Study:
- To review the key aspects of human BPD pathophysiology and phenotype relevant for animal model selection.
- To discuss the advantages and limitations of various animal models used in BPD research.
- To guide the selection of appropriate animal models for different stages of BPD research, from hypothesis generation to clinical translation.
Main Methods:
- Literature review of existing animal models for bronchopulmonary dysplasia.
- Analysis of how well animal model phenotypes and pathopysiology align with human BPD.
- Evaluation of the translational relevance of different animal models based on their characteristics.
Main Results:
- Prematurity is a core factor in BPD, making preterm animal models highly relevant.
- While oxygen, ventilation, and infection can exacerbate lung injury, they are not essential for BPD development in models.
- Animal models exhibit key BPD features like alveolar developmental arrest, airway obstruction, and pulmonary vascular disease.
- Different models offer unique advantages: term rodents for basic research, preterm large animals for clinical translation, and preterm rabbits as a versatile intermediate model.
Conclusions:
- Animal models are indispensable tools for understanding BPD and testing interventions.
- The choice of animal model should consider its ability to replicate human BPD features and its suitability for the research question.
- Careful interpretation of results, considering model-specific advantages and disadvantages, is essential for successful translation to clinical practice.
Abstract:
Bronchopulmonary dysplasia (BPD) remains a frequent and disabling consequence of preterm birth, despite the recent advances in neonatal intensive care. There is a need to further improve outcomes and many novel therapeutic or preventive strategies are therefore investigated in animal models. We discuss in this review the aspects of human BPD pathophysiology and phenotype, which ideally should be mimicked by an animal model for this disease. Prematurity remains the common denominator in the heterogeneous spectrum of human BPD, and preterm animal models thus have a clear translational advantage. Additional factors, like excessive oxygen, mechanical ventilation and infection, which frequently have been studied in animal models, can contribute to preterm lung injury however are not indispensable to develop BPD. The phenotype of human BPD is characterized by alveolar developmental arrest with extracellular matrix remodeling, signs of obstructive airway disease and pulmonary vascular disease. Many animal models mimic this phenotype and have their place in BPD research, but results should be interpreted bearing in mind the specific advantages and disadvantages of the model. Term mice and rats are well suited for basic explorative research on specific disease mechanisms, essential for the generation of new hypotheses, while the larger ventilated preterm baboons and lambs provide a good platform for the ultimate translation of these strategies towards clinical application. The preterm rabbit model seems a promising model as it the smallest model that includes a factor of prematurity and has a unique position between the small and large animal models.
