Investigating tuberculosis by engineering human granulomas

Aims

This research aims to develop a 3D in vitro model of tuberculosis granuloma formation, replacing the need for some studies in animal models.

Background

Tuberculosis (TB) remains a global health pandemic, killing almost two million people per year worldwide. It is caused by various strains of mycobacteria, usually Mycobacterium tuberculosis and is increasingly resistant to current treatments. Tuberculosis research relies heavily on the use of animal models, to both study disease mechanisms and new treatments. No current model accurately reflects disease in man.

A key pathological feature of TB infection is the formation of granulomas in the lungs - nodules where macrophages ‘wall off’ the infection. A novel in vitro granuloma model of TB infection, using human cells and extracellular matrix components, would permit the study of complex in vivo events, potentially better reflecting human disease and replacing the need for some animal studies.

Research details and methods

Using bioelectrospray technology, spheroids will be generated which incorporate primary human cells, Mycobacterium tuberculosis and extracellular matrix components. A number of parameters will be investigated to determine their effect on the host response to infection, including different mycobacterial strains and cells from patients with TB. The spheroids will subsequently be developed as a potential platform for anti-mycobacterial drug screening, potentially further replacing the use of animals.