Researchers at the Department of Bioengineering (BE) at the Indian Institute of Science (IISc) have developed a promising 3D hydrogel culture system aimed at tackling drug-resistant tuberculosis (TB) and shortages of TB medicines. This innovation, which has been patented in India, could potentially revolutionize drug testing and discovery in the pharmaceutical industry.
The new 3D culture systems are designed to closely mimic the natural environment of TB infections, offering researchers deeper insights into how Mycobacterium tuberculosis (MTB) responds to various drugs. According to IISc, this advancement could expedite the identification of effective treatments crucial for addressing both drug resistance issues and the scarcity of TB medicines.
TB, caused by MTB, remains a significant global health threat, particularly affecting the lungs. In 2022, the World Health Organization (WHO) reported that MTB affected 10.6 million people and led to 1.3 million deaths. Recently, the US Center for Disease Control and Prevention (CDC) introduced a new TB treatment regimen, underscoring ongoing efforts to combat the disease. Mumbai’s JJ Hospital also highlighted Bedaquiline as a major breakthrough in TB drug development, particularly for pediatric patients in India.
Rachit Agarwal, Associate Professor at BE, IISc and lead author of the study published in Advanced Healthcare Materials, explained that conventional MTB culture models have limitations due to their inability to accurately replicate the 3D microenvironment inside the lungs. Vishal Gupta, a PhD student and first author, emphasized that existing 2D culture plates fail to mimic the extracellular matrix (ECM) surrounding lung tissue, crucial for understanding MTB behavior.
To address this gap, the research team developed a novel 3D hydrogel culture using collagen, a key ECM molecule found in lung cells. This innovation allowed mammalian cells to remain viable for up to three weeks, a significant improvement over traditional cultures that sustain cells for only 4-7 days. Agarwal noted that this extended viability is critical given MTB’s slow growth rate in the body.
Furthermore, RNA sequencing of lung cells grown in the hydrogel revealed similarities to human samples, validating the system’s biological relevance. The researchers also demonstrated the effectiveness of pyrazinamide, a common TB drug, in clearing MTB within the hydrogel culture, showcasing the system’s potential for drug testing.
Looking ahead, the team aims to simulate granulomas—clusters of infected white blood cells—in the 3D hydrogel culture to explore latent TB mechanisms versus active symptoms. This research could provide insights into pyrazinamide’s mode of action, potentially leading to the discovery of new TB treatments.
The development marks a significant stride in TB research, promising advancements in understanding the disease and developing effective therapies using innovative 3D culture technology.