Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids

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Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids

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Title: Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids
Author: Ankrum, James A.; Dastidar, Riddhi G.; Ong, Joon Faii; Levy, Oren; Karp, Jeffrey M.

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Citation: Ankrum, James A., Riddhi G. Dastidar, Joon Faii Ong, Oren Levy, and Jeffrey M. Karp. 2014. “Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids.” Scientific Reports 4 (1): 4645. doi:10.1038/srep04645. http://dx.doi.org/10.1038/srep04645.
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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.
Published Version: doi:10.1038/srep04645
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982175/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12152931
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