Bengaluru: In an advancement for tuberculosis research, scientists at Indian Institute of Science created a novel 3D hydrogel culture system that closely mimics the human lung. This provides a platform to track and study how tuberculosis bacteria infect lung cells and test the efficacy of therapeutics used to treat the infection.
Mycobacterium tuberculosis (Mtb) is a dangerous pathogen.In 2022, it affected 10.6 million people and caused 1.3 million deaths, according to World Health Organisation.
Led by Rachit Agarwal, associate professor at the department of bioengineering, the IISc team addressed limitations of traditional 2D culture models. These older models fail to replicate the complex 3D structure of lung tissue, potentially skewing research results. “It is a very old bug, and it has evolved with us quite a bit,” said Agarwal, who’s a corresponding author of the study, published in Advanced Healthcare Materials.
The new hydrogel culture is composed of collagen, a key component of lung tissue. This 3D environment allows researchers to observe how TB bacteria interact with human immune cells over extended periods – up to three weeks, compared to just 4-7 days in conventional systems. Notably, RNA sequencing revealed that cells grown in the hydrogel more closely resemble actual human lung tissue samples than those in traditional cultures. This increased biological accuracy could lead to more relevant research outcomes. The team also demonstrated the model’s potential for drug testing. They found that a common TB drug, pyrazinamide, was effective at much lower, more clinically relevant doses than typically required in 2D cultures.
The researchers have filed an Indian patent for their innovation, which they designed to be easily replicable by other scientists and scalable for industrial drug testing.
Breakthrough can expedite further research
Future plans include using the model to study why TB manifests differently among patients and to explore new drug development possibilities. This breakthrough could accelerate TB research and potentially, lead to more effective treatment. Vishal Gupta, PhD student and first author, said the team is also interested in understanding the mechanism of the action of pyrazinamide, which may help discover new drugs that are more or just as efficient.
Mycobacterium tuberculosis (Mtb) is a dangerous pathogen.In 2022, it affected 10.6 million people and caused 1.3 million deaths, according to World Health Organisation.
Led by Rachit Agarwal, associate professor at the department of bioengineering, the IISc team addressed limitations of traditional 2D culture models. These older models fail to replicate the complex 3D structure of lung tissue, potentially skewing research results. “It is a very old bug, and it has evolved with us quite a bit,” said Agarwal, who’s a corresponding author of the study, published in Advanced Healthcare Materials.
The new hydrogel culture is composed of collagen, a key component of lung tissue. This 3D environment allows researchers to observe how TB bacteria interact with human immune cells over extended periods – up to three weeks, compared to just 4-7 days in conventional systems. Notably, RNA sequencing revealed that cells grown in the hydrogel more closely resemble actual human lung tissue samples than those in traditional cultures. This increased biological accuracy could lead to more relevant research outcomes. The team also demonstrated the model’s potential for drug testing. They found that a common TB drug, pyrazinamide, was effective at much lower, more clinically relevant doses than typically required in 2D cultures.
The researchers have filed an Indian patent for their innovation, which they designed to be easily replicable by other scientists and scalable for industrial drug testing.
Breakthrough can expedite further research
Future plans include using the model to study why TB manifests differently among patients and to explore new drug development possibilities. This breakthrough could accelerate TB research and potentially, lead to more effective treatment. Vishal Gupta, PhD student and first author, said the team is also interested in understanding the mechanism of the action of pyrazinamide, which may help discover new drugs that are more or just as efficient.
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