Researchers will team up to develop pulmonary fibrosis stem cell models
Joint effort aims to ID new treatment targets to slow disease progression
The Center for Regenerative Medicine (CReM) of Boston University and Boston Medical Center will collaborate with GSK to develop stem cell-based models to better understand pulmonary fibrosis and identify new targets for treatments that may halt or slow its progression.
“This exciting collaboration with GSK will help … make meaningful progress in the treatment of chronic lung diseases like pulmonary fibrosis,” Darrell Kotton, MD, CReM’s founding director and a professor of medicine at Boston University, said in a university news story.
With funding from GSK, the collaboration is planned for three years, but the researchers say they’d like to see it go longer.
“Together with GSK, we are poised to advance emerging research discoveries into real-world therapies for patients,” Kotton said.
Pulmonary fibrosis causes scarring and stiffening of the tiny air sacs in the lungs, known as alveoli, making it difficult for patients to breathe. Over time, the scarring gets worse and the disease becomes more challenging to treat.
Kotton’s research team has been working with induced pluripotent stem cells, or iPSCs, derived from adult blood cells. By activating specific genes, these blood cells are turned back to an embryonic stem cell-like state that can develop toward any cell type.
Researching stem cells in PF
Guiding the stem cells to become lung cells lets researchers watch how pulmonary fibrosis unfolds and figure out where they can intervene to stop it from getting worse or slow its progression. Working with GSK, the researchers will expand their bank of patient stem cells and use these to model the disease in the lab.
“I give the analogy of a black box flight recorder, because you can replay all the events that led to the malfunction over and over,” Kotton said. “You can understand the disease and then you can intervene at the set points where you want to stop the progression — and that’s where the drug development action is.”
The stem cells can also be used to repopulate the airways of patients with healthy lung cells through a transplant.
“We’re very excited and making rapid progress in that, but it’s a long way off,” Kotton said, adding that new treatments may advance into clinical testing “sooner than we think.”
For Kaivan Khavandi, MD, PhD, senior vice president and global head of respiratory/immunology research and development at GSK, advancing new treatments requires “a deep understanding of the genetic and cellular basis of disease.”
In pulmonary fibrosis, the epithelial cells that line the airways go awry and trigger scarring by sending signals to cells of mesenchymal lineage, such as fibroblasts, the cells that lay down components of the matrix that supports tissues in the body.
Together with GSK, the Boston-based research team will explore the genetic and environmental factors that stress alveolar type 2 cells — a type of cell that repopulates the lung epithelial lining after it has sustained damage — and combine them with stem cell-derived mesenchymal cells to better mimic the disease.
“Studying the crosstalk of lung epithelial and mesenchymal lineages using patient-derived stem cell and organoid [miniaturized organ]-based model systems represents an exciting new direction for the field,” Kotton said in a press release from Boston Medical Center.
CReM’s work also seeks to address health disparities, particularly among Black patients, who tend to have worse outcomes in pulmonary fibrosis. By focusing on equitable research, the collaboration hopes to develop treatments that benefit all patients.
“Black patients with pulmonary fibrosis have worse health outcomes at younger ages compared to Hispanic or white patients,” said Megan Bair-Merritt, MD, chief scientific officer of Boston Medical Center. “The collaboration with GSK will inform the development of new treatments for lung diseases that help address these disparities and pave the way for a healthier future for everyone.”
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