Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids
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Ankrum-2014-Performance-enhanced mesenchymal.pdf
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Author(s)
Ankrum, James Allen
Dastidar, Riddhi G.
Ong, Joon Faii
Levy, Oren
Karp, Jeffrey Michael
Date Issued
April 2014
Journal
Scientific Reports
Publisher
Nature Publishing Group
Citation
Ankrum, James A., Riddhi G. Dastidar, Joon Faii Ong, Oren Levy, and Jeffrey M. Karp. “Performance-Enhanced Mesenchymal Stem Cells via Intracellular Delivery of Steroids.” Sci. Rep. 4 (April 10, 2014).
Version
Final published version
Abstract
Inadequate immunomodulatory potency of mesenchymal stem cells (MSC) may limit their therapeutic efficacy. We report glucocorticoid steroids augment MSC expression and activity of indoleamine-2,3-dioxygenase (IDO), a primary mediator of MSC immunomodulatory function. This effect depends on signaling through the glucocorticoid receptor and is mediated through up-regulation of FOXO3. Treatment of MSCs with glucocorticoids, budesonide or dexamethasone, enhanced IDO expression following IFN-γ stimulation in multiple donors and was able to restore IDO expression in over-passaged MSCs. As IDO enhancement was most notable when cells were continuously exposed to budesonide, we engineered MSC with budesonide loaded PLGA microparticles. MSC efficiently internalized budesonide microparticles and exhibited 4-fold enhanced IDO activity compared to budesonide preconditioned and naïve MSC, resulting in a 2-fold improvement in suppression of stimulated peripheral blood mononuclear cells in an IDO-dependent manner. Thus, the augmentation of MSC immune modulation may abrogate challenges associated with inadequate potency and enhance their therapeutic efficacy.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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Creative Commons Attribution-Non-Commercial-NoDerivs license
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DOI of Published Version
https://doi.org/10.1038/srep04645
