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bioRxiv · 10.1101/855270

Dose and duration of IFNγ pre-licensing interact with donor characteristics to influence the expression and function of IDO in MSCs

Boyt, D.·Boland, L. K.·Burand, A. J.·Brown, A. J.·Ankrum, J. A.
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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 gamma 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 the dose of interferon gamma, the duration of pre-licensing, and the donor of origin plays 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 interferon gamma 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.

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Boyt, D., Boland, L. K., Burand, A. J., Brown, A. J., Ankrum, J. A.. 2019-11-26. Dose and duration of IFNγ pre-licensing interact with donor characteristics to influence the expression and function of IDO in MSCs. https://doi.org/10.1101/855270

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