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Updated: Feb 19, 2026
Development of a Neonatal Piglet Acute Lung Injury Model Recreating the Early Environment of Preterm Infant Lungs
Published on: October 31, 2025
Human amnion cells reverse acute and chronic pulmonary damage in experimental neonatal lung injury
Dandan Zhu1,2, Jean Tan1,2, Amina S Maleken1,2
1The Ritchie Centre, Hudson Institute of Medical Research, Clayton, VIC, Australia.
Insights
Early administration of human amnion epithelial cells (hAECs) effectively treats bronchopulmonary dysplasia (BPD) in preclinical models, improving long-term cardiorespiratory function. Intravenous or intratracheal delivery showed similar efficacy, with early treatment yielding superior outcomes.
Area of Science:
- Neonatal Medicine
- Regenerative Medicine
- Pulmonary Research
Background:
- Bronchopulmonary dysplasia (BPD) remains a major cause of infant mortality and morbidity despite advances in neonatal care.
- Human amnion epithelial cells (hAECs) show therapeutic promise for BPD, but optimal administration strategies and long-term benefits require further investigation.
- Preclinical models are crucial for evaluating hAEC therapy for BPD, focusing on dosage, route, and timing.
Purpose of the Study:
- To investigate the impact of cell dosage, administration routes, and timing of human amnion epithelial cell (hAEC) treatment in a preclinical model of bronchopulmonary dysplasia (BPD).
- To assess the long-term cardiorespiratory benefits of hAEC therapy in a BPD model.
- To compare the efficacy of early versus late administration of hAECs.
Main Methods:
- A preclinical model of BPD was established using intra-amniotic lipopolysaccharide followed by postnatal hyperoxia.
- Human amnion epithelial cells (hAECs) were administered either early (12 hours) or late (4 days) after hyperoxia onset.
- Lung tissues, immune cell populations, inflammatory markers, lung function, and cardiac function were assessed at various neonatal and juvenile time points.
Main Results:
- hAECs improved lung tissue structure in a dose-dependent manner, irrespective of administration route (intravenous or intratracheal).
- Early hAEC administration significantly reduced inflammatory markers and immune cell infiltration, leading to improved lung function and prevention of pulmonary hypertension and right ventricle hypertrophy.
- Late hAEC administration was less effective, indicating that early intervention is critical for optimal therapeutic outcomes.
Conclusions:
- Early administration of hAECs is more advantageous than late treatment for bronchopulmonary dysplasia (BPD).
- Intravenous and intratracheal routes of hAEC administration demonstrate comparable efficacy.
- hAEC treatment provides long-term improvements in cardiorespiratory function, highlighting its potential as a therapeutic strategy for BPD.
Background:
Despite advances in neonatal care, bronchopulmonary dysplasia (BPD) remains a significant contributor to infant mortality and morbidity. While human amnion epithelial cells (hAECs) have shown promise in small and large animal models of BPD, there is scarce information on long-term benefit and clinically relevant questions surrounding administration strategy remain unanswered. In assessing the therapeutic potential of hAECs, we investigated the impact of cell dosage, administration routes and timing of treatment in a pre-clinical model of BPD.
Methods:
Lipopolysaccharide was introduced intra-amniotically at day 16 of pregnancy prior to exposure to 65% oxygen (hyperoxia) at birth. hAECs were administered either 12 hours (early) or 4 days (late) after hyperoxia commenced. Collective lung tissues were subjected to histological analysis, multikine ELISA for inflammatory cytokines, FACS for immune cell populations and 3D lung stem cell culture at neonatal stage (postnatal day 7 and 14). Invasive lung function test and echocardiography were applied at 6 and 10 weeks of age.
Results:
hAECs improved the tissue-to-airspace ratio and septal crest density in a dose-dependent manner, regardless of administration route. Early administration of hAECs, coinciding with the commencement of postnatal hyperoxia, was associated with reduced macrophages, dendritic cells and natural killer cells. This was not the case if hAECs were administered when lung injury was established. Fittingly, early hAEC treatment was more efficacious in reducing interleukin-1β, tumour necrosis factor alpha and monocyte chemoattractant protein-1 levels. Early hAEC treatment was also associated with reduced airway hyper-responsiveness and normalisation of pressure-volume loops. Pulmonary hypertension and right ventricle hypertrophy were also prevented in the early hAEC treatment group, and this persisted until 10 weeks of age.
Conclusions:
Early hAEC treatment appears to be advantageous over late treatment. There was no difference in efficacy between intravenous and intratracheal administration. The benefits of hAEC administration resulted in long-term improvements in cardiorespiratory function.
