Understanding resilience, or the ability of injured lung tissue to heal and regenerate, may prove crucial for advancing treatments and preventing life-threatening lung diseases in extremely premature infants. A recent study by researchers at Vanderbilt University and Vanderbilt University Medical Center has taken a groundbreaking step forward.
The team utilized four-dimensional microscopy techniques to create 3D video images of mouse lung tissue grown in the laboratory. This live-imaging approach enabled them to observe how lungs form and quantify cellular movements, providing insight into organ development with enough surface area for gas exchange. “For the first time, we’ve been able to see the living lung as it forms and measure those essential cellular interactions that create a functional organ,” explained Jennifer Sucre, MD, Associate Professor of Pediatrics and Cell & Developmental Biology at Vanderbilt University Medical Center.
The findings were published on February 24th in JCI Insight, the journal of the American Society for Clinical Investigation. These results represent a significant milestone towards improving treatments and preventing bronchopulmonary dysplasia (BPD), which affects about half of infants born two to four months prematurely.
“If we can comprehend how lungs develop, we’ll have a blueprint for regenerating new lung tissue after injuries,” said the paper’s first author, Nick Negretti, PhD, a senior post-doctoral fellow in Sucre’s lab who co-led the research. “Mice possess remarkable abilities to repair their lungs,” added Sucre, who directs the Biodevelopmental Origins of Lung Disease (BOLD) Center at VUMC. She emphasized her goal of giving premature babies “the superpower of the mouse.”
Infants with BPD require oxygen and mechanical ventilation in early life to support breathing. However, while these treatments aid respiration initially, they can also damage delicate lung tissue. Though many such infants can be weaned off ventilators after a few days, they remain at higher risk of developing serious respiratory issues later on, including chronic obstructive pulmonary disease.
Respiration occurs in the alveoli of lungs through exchange between oxygen and carbon dioxide across a fragile basement membrane separating epithelial cells and blood vessels. The conventional view held that ingrowing septa divide airspaces into alveoli as they emerge from a layer containing epithelial, endothelial, and mesenchymal cells.
However, when the researchers imaged living neonatal mouse lung slices over three days using their innovative technology, they uncovered an alternative process: ballooning outgrowth of epithelial cells supported by rings of myofibroblasts—cells that promote tissue formation. This discovery not only offers new insight into lung development but also serves as a tool for identifying molecules and pathways guiding this regenerative process.
Moreover, it represents a breakthrough in finding drugs capable of promoting tissue regeneration after injury. Sucre’s lab remains focused on understanding the resilient mechanisms at play within mice lungs that enable them to repair damage post-infection or injury. “We want to know what specific pathways these powerful mouse lungs use for self-repair,” she said, emphasizing their goal of replicating such resilience in human infants.
