Today, new antifibrotic drugs for idiopathic pulmonary fibrosis (IPF) are tested in mice with the bleomycin-induced lung-injury and lung fibrosis model. Nevertheless, the resulting fibrotic lung of rodents is different from the fibrotic lung of IPF patients. Therefore, many drug candidates successful in the bleomycin model often fail in later clinical trials. The reasons for this are interspecies differences and difference between IPF, which is slow and irreversible in humans compared to the sharp and acute effect of the bleomycin injury to the mouse lung. Despite these shortcomings, the mouse model is in widespread use because there are no suitable alternatives. However, advances in organ-on-a chip technology make it possible to develop a credible, in-vitro IPF model to replace the bleomycin model.
This project will create an advanced in-vitro IPF model based on the lung-on-chip technology recently developed at the ARTORG Center in collaboration with the Pneumology and the Thoracic Surgery Departments of the Inselspital, Bern University Hospital. Using patients’ lung alveolar epithelial cells and diseased human lung fibroblasts, we will:
- Establish an IPF-on-chipmodel based on the lung-on-chip technology
- Develop read-outs that provide relevant information about the fibrotic process
- Test anti-fibrotic compounds in collaboration with biopharma partners in our network
Our new IPF-on-chip model will use patient cells to generate clinically relevant information, more closely resembling what happens in the lungs of an IPF sufferer. IPF-on-chip will also have use beyond simple drug discovery in biopharma. It will permit the investigation of the underlying disease mechanisms of IPF and could be used in determining the treatment regimen for IPF patients through precision medicine applications.
“The two species vary widely in their physiology and in their response to pulmonary drugs,” explains Guenat. “In humans, idiopathic pulmonary fibrosis is a progressive disease, whereas it is chemically-induced and reversible in mice. So, we cannot easily transfer test results from one to another.” “Our research contributes to advancing non-animal models and at the same time to providing each patient with the best possible therapy,” says Guenat.
Prof. Olivier Guenat
ARTORG Center for Biomedical Engineering Research, University of Bern
Prof. Thomas Geiser
Pneumology Department, Inselspital, Bern University Hospital