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NC3Rs: National Centre for the Replacement Refinement & Reduction of Animals in Research
Pilot study grant

Investigating tuberculosis by engineering human granulomas

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At a glance

Completed
Award date
July 2013
Grant amount
£74,450
Principal investigator
Dr Liku Tezera
Institute
University of Southampton

R

  • Replacement
Read the abstract
View the grant profile on GtR

Overview

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.

Publications

  1. Bielecka MK et al. (2017). A Bioengineered Three-Dimensional Cell Culture Platform Integrated with Microfluidics To Address Antimicrobial Resistance in Tuberculosis. mBio 8(1). doi: 10.1128/mBio.02073-16
  2. Tezera LB et al. (2017). Bioelectrospray methodology for dissection of the host-pathogen interaction in human tuberculosis. Bio Protoc. 7(14): pii: e2418 doi: 10.21769/BioProtoc.2418
  3. Tezera LB et al. (2017). Dissection of the host-pathogen interaction in human tuberculosis using a bioengineered 3-dimensional model. eLife 6:e21283 doi: 10.7554/eLife.21283
  4. Walker NF et al. (2017). Matrix Degradation in Human Immunodeficiency Virus Type 1-Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study. Clinical Infectious Diseases 65(1):121-132. doi: 10.1093/cid/cix231
  5. Al Shammari B et al. (2015). The extracellular matrix regulates granuloma necrosis in tuberculosis. J Infect Dis 212(3):463-73. doi: 10.1093/infdis/jiv076