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Updated: Dec 31, 2025
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Published on: May 4, 2020
Late Rescue Therapy with Cord-Derived Mesenchymal Stromal Cells for Established Lung Injury in Experimental
Megan O'Reilly1,2,3, Marius A Möbius1,2, Arul Vadivel4
1Department of Pediatrics, University of Alberta, Edmonton, Canada.
Insights
Mesenchymal stromal cells (MSCs) show potential for treating adult bronchopulmonary dysplasia (BPD) lung injury. Multiple doses or early adult administration improved lung structure and vessel density in a rat model.
Area of Science:
- Pulmonary Medicine
- Regenerative Medicine
- Neonatal Research
Background:
- Bronchopulmonary dysplasia (BPD) is a chronic lung disease resulting from extreme prematurity with lifelong impacts.
- Mesenchymal stromal cells (MSCs) are known to prevent lung injury in neonatal rodent models of BPD.
- The efficacy of MSC therapy for established lung injury in adult BPD remains unexplored.
Purpose of the Study:
- To investigate the potential of human umbilical cord-derived MSCs to restore lung growth and vascularity in adult rats with established experimental BPD.
- To determine the optimal timing and dosage regimen for MSC therapy in adult BPD.
Main Methods:
- Experimental BPD was induced in newborn rats via hyperoxia (95% O2, days 4-14).
- Adult rats (3 or 6 months old) received a single intratracheal MSC dose (1x10^6 cells/kg) or multiple doses later in adulthood.
- Lung histology was assessed at 5 or 8 months for alveolar structure and vessel density.
Main Results:
- Oxygen-exposed adult rats showed persistent BPD-like lung injury, including arrested alveolarization and reduced vessel density.
- A single MSC dose at 3 months partially improved alveolar injury and vessel density by 5 months.
- A single MSC dose at 6 months had no significant effect, but multiple doses administered from 6 to 7.5 months significantly attenuated injury and improved vascularity by 8 months.
Conclusions:
- MSC therapy can potentially ameliorate established lung injury in adult BPD.
- Treatment efficacy is dependent on the timing and dosage regimen, with multiple doses or earlier intervention in adulthood showing greater benefit.
Abstract:
Bronchopulmonary dysplasia (BPD), the main complication of extreme prematurity, has lifelong consequences for lung health. Mesenchymal stromal cells (MSCs) prevent lung injury in experimental BPD in newborn rodents when given in the immediate neonatal period. Whether MSC therapy can restore normal lung growth after established lung injury in adulthood is clinically relevant, but currently unknown. Experimental BPD was achieved by exposing newborn rats to 95% O2 from postnatal days 4-14. Human umbilical cord-derived MSCs were intratracheally administered to rats (1 × 106cells/kg body weight) as a single dose at 3 or 6 months of age followed by assessment at 5 or 8 months of age, respectively. Lung alveolar structure and vessel density were histologically analyzed. O2-exposed rats exhibited persistent lung injury characterized by arrested alveolar growth with airspace enlargement and a lower vessel density at both 5 and 8 months of age compared with controls. Single-dose MSC treatment at 3 months partially attenuated O2-induced alveolar injury and restored vessel density at 5 months. Treatment with a single dose at 6 months did not attenuate alveolar injury or vessel density at 8 months. However, treatment with multiple MSC doses at 6, 6.5, 7, and 7.5 months significantly attenuated alveolar injury and improved vessel density at 8 months of age. Treatment of the adult BPD lung with MSCs has the potential to improve lung injury if administered in multiple doses or at an early stage of adulthood.
