Researchers at the Perelman School of Medicine at the University of Pennsylvania, Cincinnati Children’s Hospital and Boston University have been awarded a $5.2 million grant, running for seven years, for collaborative work to explore mechanisms of lung regeneration in diseases such as cystic fibrosis.
The grant, one of seven awarded by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) to researchers across several fields, will cover the work of the new Progenitor Cell Translational Consortium. Together, seven teams will receive a total of $40 million over seven years to develop treatments based on stem or progenitor cells for lung, heart, and blood diseases in children and adults.
The Penn team will be headed by Edward Morrisey, PhD, the Robinette Foundation Professor of Medicine, a professor of Cell and Developmental Biology, and the director of the Penn Center for Pulmonary Biology.
“The aim of our consortium is to harness the innate power of stem and progenitor cells in the lung to promote repair and regeneration and target them using emerging techniques for promoting tissue regeneration,” Morrisey, who is also the scientific director of the Penn Institute for Regenerative Medicine, said in a news release.
The multidisciplinary team will focus on children with diseases such as cystic fibrosis, and examine if new methods, such as gene editing, can be used to treat lung disease soon after birth. They will also explore the regenerative potential of progenitor cells in adults with chronic lung disease or acute injury.
Team members have homed in on a specific type of progenitor cell, called alveolar type 2 (AT2). These cells, along with AT1 cells, line lung alveoli — the tiny structures in the lungs where the blood is oxygenated — and they produce a surfactant. This substance allows the expansion and shrinkage of the lungs during breathing, and protects the tissue from infections.
AT2 cells can also replace old or worn-out lung cells, including AT1s, explaining the interest of the Penn team. Researchers will examine the cells in detail, to better understand how they contribute to repair and regeneration.
Such information is needed to assess whether the cells might be a suitable target for gene editing techniques to strengthen their regenerative capacity, or if disease-causing mutations can be targeted in these cells.
Researchers will also focus on the role played by a specific gene, called ABCA3, in AT2 cell biology. Mutations in the ABCA3 gene can lead to severe acute and chronic pulmonary diseases in infants and children.
“Using disease-inducing ABCA3 mutations as a paradigm for congenital lung disease, we will target AT2 cells to correct these mutations as well as attempt to promote lung regeneration,” Morrisey said. “Ultimately, we hope to use lung stem and progenitor cells for treatment of various forms of lung disease.”