Researchers at the NIHR Respiratory Biomedical Research Unit have developed a new 3D system to study human infection in the laboratory.
Understanding the bacteria that cause tuberculosis (TB) in people better is the target for researchers using a new method, growing tiny spheres of infected lung tissue in the lab.
TB kills 1.8 million people each year. A bacterial infection of the lungs, symptoms include a fever and a persistent cough that lasts for weeks, sometimes causing people to cough up blood.
This latest research, funded by the Medical Research Council and published in the journal eLife, provides a new method for researchers to study how TB develops and test potential treatments.
Creating the spheres
By creating spheres of infected lung tissue, laboratory studies may more closely resemble conditions in the body. In order to tackle the technical challenges a diverse team of infectious disease researchers, engineers and bioinformaticians from Southampton and University College London came together.
They used a technique known as electrostatic encapsulation to make tiny spheres of collagen – a connecting tissue in the body – and human lung cells.
Using a particular collagen matrix to mimic the environment found in a human lung meant they were able to create conditions for the lung cells that more closely reflected events in patients than similar 2D techniques, using single-layers of cells in laboratory dishes.
Using this model and infecting the cells with TB, they could investigate what happens in a human body when TB develops. In the long term, they hope to use it to identify new antibiotic treatments and vaccines.
A better model
These spheres have many advantages as a model of TB over the standard 2D systems, providing an environment that is more similar to the inside of an infected lung.
Using the spheres, the researchers were able to study aspects not possible in other 2D model systems, such as testing whether antibiotics can successfully kill the bacteria and treat the infection.
The 3D spheres also enable experiments to be conducted for a much longer period, lasting up to three weeks - more than four times longer than standard 2D model systems. This enables research investigating how the infection develops and the effect of treatments over time.
The next phase
The next phase of the research will be in collaboration with the African Health Research Institute in Durban, in a project being funded by an MRC Global Challenges Research Fund Foundation Award worth £350,000.
Durban has a very high incidence of TB, and ideal laboratory infrastructure to introduce the 3D model to study cells from patients at high risk of developing the disease.