Researchers at the Department of Bioengineering (BE) at the Indian Institute of Science (IISc), Bengaluru have designed a new 3D hydrogel culture system that mimics the mammalian lung environment. It provides a powerful platform to track and study tuberculosis (TB) bacteria (Mycobacterium tuberculosis or MTB) infect lung cells and test the efficacy of therapies used to treat TB.
Current culture model used for the study MTB Infections have several limitations. They are typically culture plates that are monolayered and do not accurately mimic the 3D microenvironment inside the lungs. The microenvironment experienced by cells in such a 2D culture is very different from the actual extracellular matrix (ECM) surrounding lung tissue.
The researchers have now created a new 3D hydrogel culture made of collagen, a key molecule in the ECM of lung cells. Collagen is water-soluble at a slightly acidic pH. As the pH increases, collagen forms fibrils that link together to form a gel-like 3D structure. During gelling, the researchers added human macrophages – immune cells involved in fighting infection – along with Mtb. This trapped both the macrophages and the bacteria in the collagen, allowing researchers to better understand how the bacteria infect the macrophages.
The team tested the effect of pyrazinamide, one of the four most common drugs given to TB patients. They found that even a small amount of the drug (10 µg/ml) was quite effective in clearing TB patients. MTB in hydrogel culture.
Moving forward, the researchers plan to mimic granulomas – clusters of infected white blood cells – in their 3D hydrogel cultures to figure out why some people have latent TB while others develop aggressive symptoms. The team is also interested in understanding the mechanism of action of pyrazinamide, which could help in the discovery of new drugs that are more or just as efficient.