Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells

Anthony J Burand; Lin Di; Lauren K Boland; Devlin T Boyt; Michael V Schrodt; Donna A Santillan; James A Ankrum

doi:10.3389/fimmu.2020.00143

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Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells

Journal article

Open access

Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells

Anthony J Burand, Lin Di, Lauren K Boland, Devlin T Boyt, Michael V Schrodt, Donna A Santillan and James A Ankrum

Frontiers in Immunology, Vol.11, 143

02/01/2020

DOI: 10.3389/fimmu.2020.00143

PMCID: PMC7052295

PMID: 32158443

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Abstract

Mesenchymal stromal cells (MSCs) are administered locally to treat sites of inflammation. Local delivery is known to cause MSCs to aggregate into “spheroids,” which alters gene expression and phenotype. While adherent MSCs are highly efficient in their inhibition of T cells, whether or not this property is altered upon MSC aggregation has not been thoroughly determined. In this study, we discovered that aggregation of MSCs into spheroids causes them to lose their T cell-suppressive abilities. Interestingly, adding budesonide, a topical glucocorticoid steroid, alongside spheroids partially restored MSC suppression of T cell proliferation. Through a series of inhibition and add-back studies, we determined budesonide acts synergistically with spheroid MSC-produced PGE2 to suppress T cell proliferation through the PGE2 receptors EP2 and EP4. These findings highlight critical differences between adherent and spheroid MSC interactions with human immune cells that have significant translational consequences. In addition, we uncovered a mechanism through which spheroid MSC suppression of T cells can be partly restored. By understanding the phenotypic changes that occur upon MSC aggregation and the impact of MSC drug interactions, improved immunosuppressive MSC therapies for localized delivery can be designed.

Immunology

Immunosuppression

budesonide

synergy

proliferation

Original Research

mesenchymal stem cells (MSCs)

T cell

Details

Title: Subtitle: Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells
Creators: Anthony J Burand
Lin Di
Lauren K Boland
Devlin T Boyt
Michael V Schrodt
Donna A Santillan
James A Ankrum
Resource Type: Journal article
Publication Details: Frontiers in Immunology, Vol.11, 143
DOI: 10.3389/fimmu.2020.00143
PMID: 32158443
PMCID: PMC7052295
NLM abbreviation: Front Immunol
eISSN: 1664-3224
Publisher: Frontiers Media S.A
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/100000968, name: American Heart Association
Language: English
Date published: 02/01/2020
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Microbiology and Immunology; Iowa Technology Institute; Obstetrics and Gynecology
Record Identifier: 9984000933202771

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