Bioengineered In vitro 3D Miniaturized Tuberculosis Mimetic Granulomas
Shilpaa Mukundan1, Pooja Singh2, Rachana Bhatt1, John Lucas1, Aditi Shah1, Matthew Tereyek1, Ranjeet Kumar2, Theresa Chang2, Claire Carter4, Selvakumar Subbian2, Biju Parekkadan1,3
1Department of Biomedical Engineering, Rutgers, The State University of New Jersey; 2Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey; 3Cancer Institute of New Jersey, New Jersey
4Center for Discovery and Innovation, Hackensack Meridian Health, New Jersey
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a global health epidemic with 1.6 million deaths in 2017. In vitro models of TB, if predictable of human pathogenesis, can help rapidly identify new biological mechanisms of latency and activation, targets of resistance, and ultimately new therapeutic interventions. However, current models are not reminiscent of human disease, particularly lacking a critical feature of a TB granulomatous reaction, a caseous center, that is a critical source of Mtb survival and poses a challenge for drug penetration to kill these bacteria. Herein, we describe a 3D human immune organoid model of TB infection, designed with high throughput application in mind, to study physiologically relevant TB granulomas in vitro. Evaluation of TB impact on immune metabolism, inflammatory reactions, and drug responses using lab and clinical Mtb strains will be presented to highlight enabling aspects of this 3D cellular model for the in vitro characterization of pathogenesis and interventions.