Cystic fibrosis (CF) is caused by a mutation of the CFTR gene. While there are many hundreds of known mutations, not all of them are currently treatable which means a significant number of CF patients lack targeted therapies.
In an effort to identify new treatments for these patients, researchers from Boston University School of Medicine (BUSM) set out to use blood cells from individuals with CF to make patient-specific induced pluripotent stem cells (iPSCs) and generate lung epithelial cells in the lab. These lung cells are functional and highly similar to the lung cells of the patient. Using these “lung cells in a dish,” they have created a novel platform to discover effective drugs for those patients who currently don’t have any treatment options.
“This model system can be used to identify new treatments for those CF patients who continue to struggle without therapies. More broadly, the functional lung cells we are able to create have the power and potential to model various lung-specific diseases including asthma, COPD, CF, primary ciliary dyskinesia, as well as viral infections,” explains lead author Andrew Berical, MD, assistant professor of medicine at BUSM.
The researchers generated lung cells from 12 different donors and tested both approved and experimental CF drugs. Cells from patients with treatable mutations showed expected responses. Cells from patients with untreatable mutations could be used to discover novel and experimental therapies, in a safe non-invasive manner.
According to Berical and Finn Hawkins, MBBCh, who is the senior author of the study, this work opens the door to wide possibilities for the use of iPSC-derived lung cells. “To generate cells (initially from a blood draw) that are similar to actual lung cells, suggests the possibility of using these cells as both a safe drug testing platform as well as a potential treatment themselves. For example if a genetic alteration (such as a CFTR mutation) can be corrected (in the lab), we may one day have the ability to make genetically-edited lung cells and put them back into a patient, thus curing them of their lung disease,” adds Berical who also is a member of the BU/BMC Center for Regenerative Medicine.
The researchers hope that by generating lung cells that are similar in makeup and function to an individual’s own lung cells, they may one day be able to discover safe, effective and life changing medications for those who continue to struggle without adequate treatments.
These findings appear online in the journal Nature Communications.
Funding for this study was provided by the National Institute of Health and the Cystic Fibrosis Foundation.