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Proc Natl Acad Sci U S A. 2017 Mar 28;114(13):E2598-E2607. doi: 10.1073/pnas.1617933114. Epub 2017 Mar 10.

Morphological features of IFN-γ-stimulated mesenchymal stromal cells predict overall immunosuppressive capacity.

Author information

1
Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993.
2
Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, MD 20993 steven.bauer@fda.hhs.gov.

Abstract

Human mesenchymal stromal cell (MSC) lines can vary significantly in their functional characteristics, and the effectiveness of MSC-based therapeutics may be realized by finding predictive features associated with MSC function. To identify features associated with immunosuppressive capacity in MSCs, we developed a robust in vitro assay that uses principal-component analysis to integrate multidimensional flow cytometry data into a single measurement of MSC-mediated inhibition of T-cell activation. We used this assay to correlate single-cell morphological data with overall immunosuppressive capacity in a cohort of MSC lines derived from different donors and manufacturing conditions. MSC morphology after IFN-γ stimulation significantly correlated with immunosuppressive capacity and accurately predicted the immunosuppressive capacity of MSC lines in a validation cohort. IFN-γ enhanced the immunosuppressive capacity of all MSC lines, and morphology predicted the magnitude of IFN-γ-enhanced immunosuppressive activity. Together, these data identify MSC morphology as a predictive feature of MSC immunosuppressive function.

KEYWORDS:

high-content imaging; immunosuppression; interferon-gamma; mesenchymal stromal cells; morphology

PMID:
28283659
PMCID:
PMC5380055
DOI:
10.1073/pnas.1617933114
[Indexed for MEDLINE]
Free PMC Article

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