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Using Experimental Models to Identify Pathogenic Pathways and Putative Disease Management Targets in Bronchopulmonary
Rory E Morty1,2
1Department of Lung Development and Remodelling, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany, rory.morty@mpi-bn.mpg.de.
Insights
Bronchopulmonary dysplasia (BPD) management needs better preclinical models. Current rodent models offer genetic tools but lack clinical relevance for studying lung development and BPD interventions.
Area of Science:
- Neonatology
- Pulmonology
- Preclinical Research
Background:
- Bronchopulmonary dysplasia (BPD) is a significant complication in preterm infants, with limited treatment options.
- Historically, animal models have aided BPD management strategies like surfactant replacement and antenatal corticosteroids.
- Recent shifts towards rodent models have advanced understanding of lung development but may limit BPD pathogenesis research.
Purpose of the Study:
- To evaluate the utility of current experimental animal models for Bronchopulmonary dysplasia (BPD) research.
- To identify limitations in existing models for studying BPD pathogenesis and therapeutic targets.
- To highlight the need for refined preclinical models that better reflect clinical BPD scenarios.
Main Methods:
- Review of historical and current experimental animal models used in Bronchopulmonary dysplasia (BPD) research.
- Analysis of the advantages and disadvantages of large animal versus rodent models in preclinical BPD studies.
- Assessment of the translational relevance of preclinical findings to clinical management of BPD.
Main Results:
- Rodent models provide genetic tools but have limited capacity for studying respiratory mechanics and hemodynamics crucial for BPD.
- Current rodent models often lack the clinical context of prematurity and infection seen in human BPD cases.
- Recent successful BPD pharmacological interventions have shown minimal reliance on preclinical data from animal models.
Conclusions:
- Existing experimental animal models, particularly rodents, have limitations in fully recapitulating Bronchopulmonary dysplasia (BPD) pathophysiology.
- There is a critical need to refine and develop new preclinical models that better mirror the complex disease processes in infants.
- Improved models are essential for effectively evaluating novel pharmacological and therapeutic interventions for BPD management.
Abstract:
Bronchopulmonary dysplasia (BPD) is a common and serious complication of preterm birth. Limited pharmacological and other medical interventions are currently available for the management of severely affected, very preterm infants. BPD can be modelled in preclinical studies using experimental animals, and experimental animal models have been extremely valuable in the development of hallmark clinical management strategies for BPD, including pulmonary surfactant replacement and single-course antenatal corticosteroids. A gradual move away from large animal models of BPD in favor of term-born rodents has facilitated the identification of a multitude of new mechanisms of normal and stunted lung development, but this has also potentially limited the utility of experimental animal models for the identification of pathogenic pathways and putative disease management targets in BPD. Indeed, more recent pharmacological interventions for the management of BPD that have been validated in randomized controlled trials have relied very little on preclinical data generated in experimental animal models. While rodent-based models of BPD have tremendous advantages in terms of the availability of genetic tools, they also have considerable drawbacks, including limited utility for studying breathing mechanics, gas exchange, and pulmonary hemodynamics; and they have a less relevant clinical context where lung prematurity and a background of infection are now rarely present in the pathophysiology under study. There is a pressing need to refine existing models to better recapitulate pathological processes at play in affected infants, in order to better evaluate new candidate pharmacological and other interventions for the management of BPD.
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