Journal article
Dose and duration of interferon γ pre-licensing interact with donor characteristics to influence the expression and function of indoleamine-2,3-dioxygenase in mesenchymal stromal cells
Journal of the Royal Society interface, Vol.17(167), pp.20190815-20190815
06/2020
DOI: 10.1098/rsif.2019.0815
PMID: 32546114
Abstract
Human mesenchymal stromal cells (MSCs) are a leading cell therapy candidate for the treatment of immune and inflammatory diseases due to their potent regulation of immune cells. MSC expression of indoleamine-2,3-dioxygenase (IDO) upon interferon γ (IFNγ) exposure has been proposed as both a sentinel marker and key mediator of MSC immunomodulatory potency. Rather than wait for in vivo exposure to cytokines, MSCs can be pre-licensed during manufacturing to enhance IDO expression. In this study, we systematically examine the relative role that the dose of IFNγ, the duration of pre-licensing and the donor of origin play in dictating MSC production of functional IDO. We find that across three human MSC donors, MSCs increase their expression of IDO in response to both increased dose of IFNγ and duration of pre-licensing. However, with extended pre-licensing, the expression of IDO no longer predicts MSCs ability to suppress activated peripheral blood mononuclear cells. In addition, pre-licensing dose and duration are revealed to be minor modifiers of MSCs inherent potency, and thus cannot be manipulated to boost poor donors to the levels of high-performing donors. Thus, the dose and duration of pre-licensing should be tailored to optimize performance of specific donors and an emphasis on donor selection is needed to realize significant benefits of pre-licensing.
Details
- Title: Subtitle
- Dose and duration of interferon γ pre-licensing interact with donor characteristics to influence the expression and function of indoleamine-2,3-dioxygenase in mesenchymal stromal cells
- Creators
- Devlin T Boyt - Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA, USA, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USALauren K Boland - Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA, USA, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USAAnthony J Burand - Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA, USA, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USAAlex J Brown - Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA, USA, Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Denver, CO, USA, Department of Biomedical Research, National Jewish Health, Denver, CO, USAJames A Ankrum - Roy J. Carver Department of Biomedical Engineering, College of Engineering, University of Iowa, Iowa City, IA, USA, Fraternal Order of Eagles Diabetes Research Center, University of Iowa, Iowa City, IA, USA
- Resource Type
- Journal article
- Publication Details
- Journal of the Royal Society interface, Vol.17(167), pp.20190815-20190815
- DOI
- 10.1098/rsif.2019.0815
- PMID
- 32546114
- NLM abbreviation
- J R Soc Interface
- ISSN
- 1742-5689
- eISSN
- 1742-5662
- Grant note
- name: Straub Foundation; DOI: 10.13039/100000002, name: National Institutes of Health, award: 1T32NS045549, 5T32GM007337
- Language
- English
- Date published
- 06/2020
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Microbiology and Immunology
- Record Identifier
- 9984000930402771
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