Content Experts Focus on Regenerating Lungs in Premature Infants with Bronchopulmonary Dysplasia

Understanding resilience, or the ability of injured lung tissue to heal and regenerate, may hold crucial keys for advancing treatments and preventing life-threatening lung diseases affecting extremely premature infants. A recent study conducted by researchers at Vanderbilt University and Vanderbilt University Medical Center has made significant strides in this field.

The team utilized a four-dimensional microscopy technique to create 3D video images of mouse lung tissue grown in the laboratory. This groundbreaking research allowed them to observe and measure cellular movements involved in organ formation for the first time, revealing how these processes contribute to a large enough surface area for gas exchange.

“For the first time, we’ve been able to live-image the lung as it forms, and quantify those cellular movements that come together to make an organ with a sufficient surface area for gas exchange,” said Jennifer Sucre, MD, Associate Professor in Pediatrics and Cell & Developmental Biology at Vanderbilt University Medical Center.

The findings from this study were published on February 24 as the cover article in JCI Insight, the journal of the American Society of Clinical Investigation. These results represent a significant step forward in developing better treatments for bronchopulmonary dysplasia (BPD), which affects approximately 50% of infants born between two and four months prematurely.

“If we can understand how the lung forms, then we have a blueprint for growing new lungs after injury,” said Nick Negretti, PhD, the first author of the paper. “Mice possess an extraordinary ability to repair their lungs.”

Sucre added, “I want to give babies the superpower of mice.” Premature infants with BPD often require oxygen and mechanical ventilation in their early days after birth. However, while these treatments help them breathe initially, they also risk damaging delicate lung tissue.

Many premature babies can be weaned off ventilators within a few days; yet, they remain at increased risk for developing serious breathing problems later in life, including chronic obstructive pulmonary disease. Respiration occurs through the alveoli of the lungs across a thin basement membrane separating epithelial cells and blood vessels.

The traditional view on lung development posited that ingrowing septa emerge from layers of epithelial, endothelial, and mesenchymal cells to divide airspaces into alveoli. However, by imaging slices of living neonatal mouse lungs over three days, the researchers discovered a different process: a ballooning outgrowth supported by a ring of myofibroblasts.

The innovative technology developed in Sucre’s lab enables testing and identification of specific molecules and pathways guiding this regenerative process. It also serves as a discovery tool for drugs that promote tissue regeneration after injury. “We’re keen to understand the resilient (mouse) lung: what are the repair mechanisms? How can we harness them?” Sucre said.