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Article

In Vitro Miniaturized Tuberculosis Spheroid Model

1
Department of Biomedical Engineering, Rutgers, The State University of New Jersey, Jersey City, NJ 08854, USA
2
Public Health Research Institute, New Jersey Medical School, Rutgers, The State University of New Jersey, Jersey City, NJ 07103, USA
3
Department Center for Discovery and Innovation, Hackensack Meridian Health, Neptune, NJ 07110, USA
4
Department of Microbiology and Immunology, School of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
5
Department of Medicine, Rutgers Biomedical Health Sciences, Rutgers, The State University of New Jersey, Jersey City, NJ 08854, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Dukjin Kang
Biomedicines 2021, 9(9), 1209; https://doi.org/10.3390/biomedicines9091209
Received: 12 July 2021 / Revised: 1 September 2021 / Accepted: 6 September 2021 / Published: 13 September 2021
Tuberculosis (TB) is a public health concern that impacts 10 million people around the world. Current in vitro models are low throughput and/or lack caseation, which impairs drug effectiveness in humans. Here, we report the generation of THP-1 human monocyte/macrophage spheroids housing mycobacteria (TB spheroids). These TB spheroids have a central core of dead cells co-localized with mycobacteria and are hypoxic. TB spheroids exhibit higher levels of pro-inflammatory factor TNFα and growth factors G-CSF and VEGF when compared to non-infected control. TB spheroids show high levels of lipid deposition, characterized by MALDI mass spectrometry imaging. TB spheroids infected with strains of differential virulence, Mycobacterium tuberculosis (Mtb) HN878 and CDC1551 vary in response to Isoniazid and Rifampicin. Finally, we adapt the spheroid model to form peripheral blood mononuclear cells (PBMCs) and lung fibroblasts (NHLF) 3D co-cultures. These results pave the way for the development of new strategies for disease modeling and therapeutic discovery. View Full-Text
Keywords: tuberculosis; lipid characterization; MALDI MSI; in vitro model tuberculosis; lipid characterization; MALDI MSI; in vitro model
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MDPI and ACS Style

Mukundan, S.; Singh, P.; Shah, A.; Kumar, R.; O’Neill, K.C.; Carter, C.L.; Russell, D.G.; Subbian, S.; Parekkadan, B. In Vitro Miniaturized Tuberculosis Spheroid Model. Biomedicines 2021, 9, 1209. https://doi.org/10.3390/biomedicines9091209

AMA Style

Mukundan S, Singh P, Shah A, Kumar R, O’Neill KC, Carter CL, Russell DG, Subbian S, Parekkadan B. In Vitro Miniaturized Tuberculosis Spheroid Model. Biomedicines. 2021; 9(9):1209. https://doi.org/10.3390/biomedicines9091209

Chicago/Turabian Style

Mukundan, Shilpaa, Pooja Singh, Aditi Shah, Ranjeet Kumar, Kelly C. O’Neill, Claire L. Carter, David G. Russell, Selvakumar Subbian, and Biju Parekkadan. 2021. "In Vitro Miniaturized Tuberculosis Spheroid Model" Biomedicines 9, no. 9: 1209. https://doi.org/10.3390/biomedicines9091209

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