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

Frontiers in Immunology
Anthony J BurandJames A Ankrum

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, impro...Continue Reading

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Citations

Sep 19, 2020·International Journal of Molecular Sciences·Santiago RouraFrancesc E Borràs
Jan 9, 2021·Stem Cell Research & Therapy·Mesude BicerDarius Widera
Mar 2, 2021·Medicinal Research Reviews·Bruna C GalgaroMárcia R Wink
May 1, 2021·Advanced Healthcare Materials·Gilad Doron, Johnna S Temenoff
May 26, 2021·Cell Biochemistry and Function·Isabele Cristiana IserMarcia Rosângela Wink

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Methods Mentioned

BETA
flow cytometry
Assay
ELISA

Software Mentioned

FlowJo
GraphPad Prism

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