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Updated: Dec 26, 2025
Assessment of the Immunomodulatory Properties of Human Mesenchymal Stem Cells MSCs
Published on: December 24, 2015
Aggregation of Human Mesenchymal Stromal Cells Eliminates Their Ability to Suppress Human T Cells
Anthony J Burand1,2, Lin Di1,2, Lauren K Boland1,2
1Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA, United States.
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.
Insights
Mesenchymal stromal cells (MSCs) lose T cell suppression when forming spheroids. Budesonide partially restores this suppression by working with MSC-produced PGE2, offering insights for localized MSC therapies.
Area of Science:
- Immunology
- Cell Biology
- Pharmacology
Background:
- Mesenchymal stromal cells (MSCs) are used for localized inflammation treatment.
- MSC aggregation into spheroids alters their gene expression and phenotype.
- The impact of MSC aggregation on T cell suppression is not fully understood.
Purpose of the Study:
- To determine if MSC aggregation into spheroids affects their T cell-suppressive abilities.
- To investigate the effect of budesonide on spheroid MSC-mediated T cell suppression.
- To elucidate the mechanism underlying budesonide's effect on spheroid MSCs.
Main Methods:
- Comparing T cell suppression by adherent MSCs versus spheroid MSCs.
- Assessing the effect of budesonide on spheroid MSCs' T cell suppression.
- Utilizing inhibition and add-back studies to identify involved pathways and receptors.
Main Results:
- MSC aggregation into spheroids significantly reduces their ability to suppress T cell proliferation.
- Budesonide partially restores the T cell-suppressive function of spheroid MSCs.
- Budesonide acts synergistically with spheroid MSC-produced PGE2 via EP2 and EP4 receptors.
Conclusions:
- MSC aggregation alters their immunomodulatory properties, impacting localized delivery efficacy.
- Budesonide can partially restore spheroid MSC immunosuppression through a synergistic mechanism with PGE2.
- These findings are crucial for designing improved MSC-based therapies for localized immunosuppression.
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