A joint research team has leveraged its organ-on-a-chip technology to develop a model of the human small airway in which lung inflammatory diseases, such as COPD and asthma, can be studied outside of the human body. The platform, which was developed by researchers at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) and the Wyss Institute for Biologically Inspired Engineering at Harvard University, will allow researchers to gain new insights into the mechanisms of the disease, identify novel biomarkers, and test new drug candidates, according to a Harvard University news report.
Donald Ingber, senior author of the study, “Inspired by our past work using the organ-on-a-chip approach to model the lung alveolus, we created a new microfluidic model of the lung small airway that recapitulates critical features of asthma and COPD with unprecedented fidelity and detail. Now with this microengineered human lung small airway, we can study lung inflammatory diseases over several weeks in chips lined by cells from both normal donors and diseased patients to gain better insight into disease mechanisms, as well as screen for new therapeutics.”
The Harvard University news report says the demand for this type of an opportunity is particularly high since small airway inflammation cannot be adequately studied in human patients or animal models.
“To closely mimic the complex 3D cellular architecture of actual human small airways, we designed a microfluidic device that contains a fully matured human small airway epithelium with different specialized cell types exposed to air in one of its two parallel microchannels. The second channel is lined by a human vascular endothelium in which we flow medium containing white blood cells and nutrients so that the living microsystem can be maintained over weeks,” says Remi Villenave, the co-first author on the publication. Villenave adds that the team then modeled inflammatory asthma and COPD conditions by adding an asthma-inducing immune factor or by setting up the system with lung epithelial cells attained from COPD patients.
Co-first author of the study Kambez Hajipouran Benam explains, “This new organ-on-a-chip technology gives us a window on molecular-scale activities in the context of living human lung tissue. It also provides us with a handle to dissect contributions of specific cell types and biochemical factors to small airway diseases.” The researcher also provided proof-of-principle that the synthetic small airway-on-a-chip can be used as a discovery platform for disease-specific drugs and biomarkers, according to the Harvard University news report. Two drugs targeting different key molecular components of inflammatory pathways can suppress pathological processes in asthma and COPD-tailored small airway chips.
Ingber says, “This novel ability to build small airway chips with cells from individual patients with diseases like COPD positions us and others now to investigate the effects of genetic variability, specific immune cell populations, pharmaceutical candidates and even pandemic viruses in an entirely new and more personalized way; one that will hopefully increase the likelihood of success of future therapeutics.”
Source: Harvard University