IISc's 3D Lung Model: A Game-Changer for TB Drug Testing in India
In a significant scientific breakthrough, researchers at the Indian Institute of Science (IISc) in Bengaluru have developed a three-dimensional lung model that could transform how India tests drugs for tuberculosis (TB). This innovative model mirrors real human lung tissue, offering a more accurate representation of TB behavior and drug responses compared to traditional lab systems.
Addressing India's TB Burden with Cutting-Edge Research
India continues to bear one of the world's largest TB burdens, with an estimated 2.5 to 3 million cases annually. The new 3D model, funded by the India Alliance—a partnership between the Department of Biotechnology and the Wellcome Trust, UK—aims to bolster the nation's fight against this persistent disease. By utilizing a soft collagen gel that replicates the texture and structure of lung tissue, the model provides mechanical and biochemical cues similar to the human lung microenvironment.
How the 3D Model Outperforms Conventional Systems
Traditional TB research has long relied on flat, two-dimensional cell cultures that fail to mimic the complexities of the human body. In contrast, the IISc team injected infected human immune cells into their 3D hydrogel model, observing behavior that closely resembles real patient scenarios. Key TB features, such as fat-filled immune cells and clusters of TB bacteria, emerged in this model, which are often missed in standard lab setups.
Dr. Rachit Agarwal, a DBT/Wellcome Trust Intermediate Fellow at IISc, highlights the model's efficacy. "This new 3D system is a much more realistic way to study TB and test new medicines that could help speed up treatments," he explains. Notably, the model successfully demonstrated the effects of the TB drug Pyrazinamide, a feat that other lab models typically fail to achieve.
Advantages Over Existing Drug Testing Models
Current methods for testing TB drug efficacy include:
- Planktonic bacterial cultures: Direct drug testing on bacterial samples.
- Two-dimensional mammalian cell cultures: Cells infected with bacteria and tested with drugs, though results may not translate effectively to humans.
- Animal models: Such as mice, but with regulatory shifts like the FDA Modernisation Act 3.0 in the USA and New Drugs and Clinical Trials Rules in India, 3D organoids and organ-on-a-chip models are now advocated as reliable alternatives.
The IISc model is modular, scalable, and adaptable for extended studies on drug efficacy and infection biology, offering a promising substitute for pre-human trial testing.
Potential for Tackling Drug-Resistant TB
India is a hotspot for drug-resistant TB, contributing significantly to global cases of multi-drug-resistant and rifampicin-resistant TB. Dr. Agarwal notes that while drug-resistant bacteria studies have not yet been conducted in this model, it holds potential. "By infecting mammalian cells in our hydrogels with drug-resistant clinical bacterial isolates, it should be possible to test and identify drugs that work against DR and XDR bacteria," he states.
Researchers are further enhancing the model to mimic tuberculosis granulomas—tight aggregates of immune cells surrounding bacteria, a hallmark of TB pathology. Such advancements could improve understanding of host-pathogen interactions and drug delivery challenges, crucial for developing effective treatments.
Implications for Future TB Research and Treatment
This 3D lung model represents a pivotal step forward in TB research, offering a more human-relevant platform for drug testing. As India strives to reduce its TB burden, innovations like this could accelerate the development of new therapies and improve outcomes for patients, particularly those with drug-resistant strains. The integration of such advanced models into standard testing protocols may soon become a cornerstone of India's healthcare strategy against tuberculosis.
