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New 3D Spheres Replicate Human Cells to Better Study Infection

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A new 3D system has been developed to enable researchers to more effectively study human infections in the laboratory.

A diverse team of infectious disease researchers, engineers and bioinformaticians from the University of Southampton and University College London came together to better understand the bacteria that cause tuberculosis (TB).

They used a technique known as electrostatic encapsulation to make tiny spheres of collagen – a connecting tissue in the body – within which human cells are infected with tuberculosis (TB) bacteria to generate conditions that more closely reflect events in patients than similar 2D techniques.

New 3D spheres replicate human cells to better study infection
Credit: BBSRC
The team developed human lung cells which were then placed in the 3D spheres and infected with tuberculosis (TB) bacteria allowing the researchers to further investigate what happens in a human body when TB develops.

Professor Paul Elkington, who leads the Southampton TB research group, commented: “This is a really exciting development for the field of tuberculosis research. The 3D sphere can be created with a collagen matrix so it is more like a human lung. This produces an environment which allows particular antibiotics that are important in treating patients to kill the infection, which they cannot do in other 2D model systems. This system will help us speed up the process of finding treatments and vaccines for human tuberculosis, an infection that kills 1.8 million people per year.”

With a long-term aim of identifying new antibiotic treatments and vaccines, the 3D spheres are also able to prolong experiments for up to three weeks, more than four times longer than standard 2D model systems. This gives researchers more information about how the infection develops and the effect of different interventions over time.

The research was funded by the Antimicrobial Resistance Cross-Council Initiative which brings together all seven UK Research Councils to develop collaborative approaches across research disciplines and to identify a number of research opportunities and challenges in tackling the rise in antimicrobial resistance.

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 tuberculosis.

Professor Elkington added: “We are delighted to extend our research and have the opportunity to combine diverse expertise to develop an advanced laboratory system that can be applied to a wide range of infections, especially the infections that are prevalent in resource-poor countries. We will use our 3D model to integrate engineering and biological approaches with clinical specimens to create an entirely new system of studying infection.”

Dr Al Leslie, of the Africa Health Research Institute, said: “There is a huge amount to be gained from infectious disease biologists and engineers working together, as they push each other out of their comfort zones and force a new perspective on the problem being tackled. This grant is the start of what we hope to be a long-term collaboration that will bring real innovation to our TB research programmes and speed up the pace of discovery to fight this deadly epidemic.”

Contacts and sources:
Biotechnology and Biological Sciences Research Council (BBSRC)

The paper: A Bioengineered 3-Dimensional Cell Culture Platform Integrated With Microfluidics to Address Antimicrobial Resistance was published in mBio (DOI:10.1128/mBio.02073-16) and in eLife as Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model.


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