Ankrum, James A.Dastidar, Riddhi G.Ong, Joon FaiiLevy, OrenKarp, Jeffrey2014-05-062014Ankrum, 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/srep04645.2045-2322http://nrs.harvard.edu/urn-3:HUL.InstRepos:12152931Inadequate 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.en-USJournal Article2014-05-0610.1038/srep04645