In Vitro Miniaturized Tuberculosis Spheroid Model

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2021 Sep 28

PMID 34572395

Citations 6

Authors

Shilpaa Mukundan

Pooja Singh

Aditi Shah

Ranjeet Kumar

Kelly C ONeill

Claire L Carter

David G Russell

Selvakumar Subbian

Biju Parekkadan

Affiliations

Soon will be listed here.

Abstract

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, (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.

Citing Articles

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[Characterization of a 3-dimensional tuberculosis spheroid model constructed using human monocytic THP-1 cells and ].

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