Idiopathic pulmonary fibrosis (IPF) is a serious chronic disease that affects the tissue surrounding the air sacs in the lungs. This condition occurs when that lung tissue becomes thick and stiff for unknown reasons. Over time, these changes can cause permanent scarring in the lungs, called fibrosis, that make it progressively more difficult to breathe.
Treatments often are ineffective and the development of novel therapeutics is hampered due to lack of available human in vitro models that are needed to understand pathogenesis or develop novel drug therapies.
In response, a team of researchers led by Darrell Kotton, MD, the David C. Seldin Professor of Medicine, has been awarded a four-year, $2.4 million U01 grant from the National Institutes of Health/National Heart, Lung, and Blood Institute to better understand the mechanisms that initiate and perpetuate this deadly disease.
Dr. Kotton plans to develop a human, three-dimensional model system for the study of IPF using a biorepository of induced pluripotent stem cells (iPSCs) that his team has generated from individuals with sporadic or familial pulmonary fibrosis to model IPF in-vitro.
Growing literature implicates lung epithelial dysfunction as playing a role in the events that lead to downstream fibroblast (cells found in connective tissue) activation, culminating in fibrosis. These studies, together with the observation that lung epithelial cells in many forms of IPF display shortened telomeres (a compound structure at the end of a chromosome), suggests that lung epithelial dysfunction may initiate IPF and accelerated aging phenotypes or telomerase pathway abnormalities likely contribute to this pathogenesis.
“Without access to patient-specific human epithelial-mesenchymal model systems, there are limited options for testing hypotheses of how epithelial changes induced by gene polymorphisms or telomerase perturbations might mechanistically contribute to IPF,” explains Dr. Kotton who also is Director of the Center for Regenerative Medicine (CReM) at BU and Boston Medical Center.
Dr. Kotton believes this work will provide insights into the development of IPF and may lead to potential new treatments.