Dataset Information

In Vitro Miniaturized Tuberculosis Spheroid Model.

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, 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.

SUBMITTER: Mukundan S

PROVIDER: S-EPMC8470281 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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In Vitro Miniaturized Tuberculosis Spheroid Model.

Mukundan Shilpaa S Singh Pooja P Shah Aditi A Kumar Ranjeet R O'Neill Kelly C KC Carter Claire L CL Russell David G DG Subbian Selvakumar S Parekkadan Biju B

Biomedicines 20210913 9

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 fact ...[more]

PMID: 34572395

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Dataset Information

In Vitro Miniaturized Tuberculosis Spheroid Model.

Publications

In Vitro Miniaturized Tuberculosis Spheroid Model.

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