3-D Lung Spheres Grown from Biopsy Tissue May Predict IPF Patient Response to Treatment

Pulmospheres — tiny, three-dimensional spheres made of lung cells taken from patients — can predict how well a person with idiopathic pulmonary fibrosis (IPF) will respond to medications commonly used to treat the disease, according to a new study.

Currently, “flat” cultures of lung cells are  used to study possible effects of drug treatments in patients. Pulmospheres, in contrast, are like “lungs on a dish”: they are cultured in the lab but grown from tissue biopsies collected from patients, contain all the various human lung cells, and are organized in a 3-D structure. As such, they allow researchers to study personalized drug therapies in an environment more closely resembling a real lung, and better examine lung diseases overall.

“Our results suggest that pulmospheres simulate the microenvironment in the lung and serve as a personalized and predictive model for assessing responsiveness to antifibrotic drugs in patients with IPF,” Veena Antony, MD, and the study’s senior author, said in a news release.

The study, “3D Pulmospheres Serve As A Personalized And Predictive Multicellular Model For Assessment Of Antifibrotic Drugs,” was published in the Journal Of Clinical Investigation.

Researchers created pulmospheres using tissue samples from 20 IPF patients and nine healthy controls, grown for one day to an adequate size (about 1 mm in diameter). Cells were then exposed to two approved IPF treatments, Esbriet (pirfenidone) and Ofev (nintedanib), to test how well a patient’s cells responded to these medications — determining which treatment works best, or works at all, for a given patient.

“There is no cure for IPF, but there are two FDA-approved drugs that can help slow the rate of decline caused by the disease and improve quality of life,” Antony said. “Not all patients respond to both drugs, and some don’t respond to either. Having a reliable clinical test that can predict which drug works best for which patient is urgently needed.” Anthony is a professor in the Division of Pulmonary, Allergy and Critical Care Medicine in the Department of Medicine at the University of Alabama Birmingham (UAB).

Within 16 hours of running tests on the pulmospheres, researchers found that three of the 20 patients responded to Ofev and four patients responded to Esbriet. The lung tissues from 11 others demonstrated sensitivity to both drugs, while those of two patients responded to neither drug. Importantly, the same results were seen when researchers followed actual patient response to these treatments, validating the predictions obtained using pulmospheres.

“This is a wonderful example of precision medicine,” said Victor Thannickal, MD, professor and director of the Division of Pulmonary, Allergy and Critical Care Medicine at UAB, and a study co-author. “Using pulmospheres derived from a patient’s own cells may allow clinicians to tailor specific drugs to an individual patient without exposing that patient to potential side-effects or harm from treatments that are unlikely to be effective.”

According to Antony, pulmospheres make it possible to test several drugs so as to identify those effective for a given IPF patient, allowing personalized medicine in the treatment of this disease. They also could aid in decisions as to which drugs to test in clinical trials.