Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids

James A Ankrum; Riddhi G Dastidar; Joon Faii Ong; Oren Levy; Jeffrey M Karp

doi:10.1038/srep04645

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Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids

Journal article

Open access

Peer reviewed

Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids

James A Ankrum, Riddhi G Dastidar, Joon Faii Ong, Oren Levy and Jeffrey M Karp

Scientific reports, Vol.4(1), pp.4645-4645

04/10/2014

DOI: 10.1038/srep04645

PMCID: PMC3982175

PMID: 24717973

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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.

Indoleamine-Pyrrole 2,3,-Dioxygenase - biosynthesis

Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism

Glucocorticoids - administration & dosage

Cell Proliferation

HLA-A Antigens - biosynthesis

HLA-C Antigens - biosynthesis

Anti-Inflammatory Agents - pharmacology

Humans

Cells, Cultured

Mesenchymal Stromal Cells - metabolism

Interferon-gamma - metabolism

Budesonide - pharmacology

Nanoparticles

Dexamethasone - pharmacology

RNA Interference

HLA-B Antigens - biosynthesis

Glucocorticoids - pharmacology

Anti-Inflammatory Agents - administration & dosage

RNA, Small Interfering

Budesonide - administration & dosage

HLA-DR Antigens - biosynthesis

Details

Title: Subtitle: Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids
Creators: James A Ankrum - 1] Center for Regenerative Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA 02139, USA
Riddhi G Dastidar - Center for Regenerative Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Joon Faii Ong - Center for Regenerative Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Oren Levy - Center for Regenerative Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
Jeffrey M Karp - 1] Center for Regenerative Therapeutics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA Harvard-MIT Division of Health Sciences & Technology, Cambridge, MA 02139, USA Harvard Stem Cell Institute, 1350 Massachusetts Avenue, Cambridge, MA 02138, USA
Resource Type: Journal article
Publication Details: Scientific reports, Vol.4(1), pp.4645-4645
DOI: 10.1038/srep04645
PMID: 24717973
PMCID: PMC3982175
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Publisher: England
Grant note: R01 HL095722 / NHLBI NIH HHS HL095722, / NHLBI NIH HHS
Language: English
Date published: 04/10/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering
Record Identifier: 9984001095702771

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