Idiopathic lung fibrosis (IPF) is a serious infectious disease that affects the material around the air sacs in the lungs. This condition occurs when that lung becomes thick and unstable for unknown reasons. Over time, these changes can cause a permanent rupture of the lungs, called fibrosis, which makes it harder to breathe.
Treatment is often ineffective and novel therapeutic development is hampered by the lack of human in vitro models needed to understand pathogenesis or develop novel drug therapies.
In response, a team of researchers led by Darrell Kotton, MD, David C. Seldin Professor of Medicine at Boston University School of Medicine (BUSM), has received a four-year, $ 2.4 million U01 grant from the National Institutes of Health / National Institute of Heart, Lung and Blood to better understand the mechanisms underlying the onset and survival of this deadly disease.
Kotton plans to develop a human three-dimensional model system for IPF analysis using a biorepository of stimulated stem cells (iPSCs) that his team generated from individuals with sporadic or familial lung fibrosis to model in-vitro IPF to model.
There is a growing literature that lung epithelial dysfunction is part of the events leading to downstream fibroblast activation (cells found in connective tissue), culminating in fibrosis. These studies, combined with the observation that lung epithelial cells in many forms of IPF exhibit abbreviated telomeres (cement structure at the end of chromosome), suggest that lung epithelial dysfunction may induce IPF and accelerated phenotypes that induce aging or telomerase pathway disorders that tend to contribute to this pathogenesis.
In the absence of access to patient-specific human epithelial-mesenchymal model systems, there are limited options for testing hypotheses on how epithelial changes caused by gene polymorphisms or telomerase mutations may contribute to mechanical to IPF. “
Darrell Kotton, MD, Director, Center for Regenerative Medicine (CReM) at BU and Boston Medical Center
Kotton believes this work will provide insight into the development of IPF and may lead to potential new therapies.
Source:
Boston University School of Medicine