Researchers have built lungs in the laboratory that more accurately emulate human lungs than traditional models, opening the door to rapid drug discovery and development and reducing reliance on animals for testing. has been reduced.
Lung disease is the leading cause of death worldwide. According to the World Health Organization (WHO), chronic obstructive pulmonary disease (COPD) is projected to become the third leading cause of death by 2030 due to poor air quality and the aftermath of COVID-19.
COPD is an incurable disease that blocks small airways in the lungs, making it difficult to breathe. Smoking and air pollution are the most common causes of COPD. Current treatments cannot reverse the damage done to lung tissue. New therapies such as stem cell-based medicines have shown the ability to repair or prevent lung deterioration, but there is a clear shortage of new therapies approved for the treatment of lung disease.
Animal models have traditionally been required to develop and test new drugs for COPD. The problem with using animals for testing is that some aspects of their anatomy and physiology differ from those of humans, and many animal models do not allow testing of aerosol drugs.
Recently, there have been advances regarding the development of alternatives to animal models. Organs-on-a-chip, organoids (3D structures grown from human cells that mimic real organs), and 3D-printed organs are good examples. However, they have drawbacks, often related to their small size, limited cell number, and lack of resemblance to the complex structures and processes found in the human lung. doing. But now, a team led by researchers at the University of Sydney has built lungs that more accurately emulate human lungs.
“Traditional cell culture puts cells in petri dishes and cultures them in a quiescent state, which is a far cry from what happens in the human body,” said Thanh Huyen Phan, lead author of the study. . “What we’re doing is creating environmental conditions similar to those that exist in the human body.”
Taking cells directly from a patient, the researchers arranged them in layers just as they would appear in the body.
“We take the cells directly from the patient and build them up in layers as they exist in the body,” said Wojciech Chrzanowski, the study’s corresponding author. “So first you have the epithelial cells and then you have the fibroblasts. We’re literally creating a mimetic organ that looks a lot like a real human lung.”
The lung model is maintained under the same environmental conditions as the real lung and has air on one side and a liquid interface on the other side combined with microcirculation that mimics the body’s circulatory system. The researcher said he created two lung models for different uses.
“We decided to build two different lung models, one mimicking a phase 1 clinical trial: a healthy lung to study the safety of new drugs,” Chrzanowski said. said. “The other mimics a phase 2 trial. In our case, diseased lungs that mirror chronic obstructive pulmonary disease, allowing us to study therapeutic efficacy and superiority of drugs.”
However, the lung model can be used for more than just drug testing.
“These mini-lung organoid models can also be used to test toxicity,” says Chrzanowski. “For example, silica dust and air pollutants such as the particulate matter produced during wildfires.”
Additionally, they can be individualized.
“Being able to take cells directly from individual patients, we can build models of their own and test the effectiveness of drugs on patients,” Chrzanowski said.
In addition to providing an alternative to animal testing, the researchers say the advantages of laboratory-made lungs are reproducibility, reliability, and the ability to enable large-scale, cost-effective studies. It is said that
“They accelerate the discovery process and shorten the path to the clinic, but they also give us much more confidence in the molecules we create before they go to clinical trials,” said Chrzanowski. “The typical timeline for clinical translation of drugs is about 10 to 15 years, but organoid models can reduce that time significantly.”
The study was published in a journal Biomaterial research.
Source: University of Sydney
