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Proc Natl Acad Sci U S A 2017 Mar 28;114(13):E2598-607

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

Klinker MW, Marklein RA, Lo Surdo JL, Wei CH, Bauer SR


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-¿ stimulation significantly correlated with immunosuppressive capacity and accurately predicted the immunosuppressive capacity of MSC lines in a validation cohort. IFN-¿ enhanced the immunosuppressive capacity of all MSC lines, and morphology predicted the magnitude of IFN-¿-enhanced immunosuppressive activity. Together, these data identify MSC morphology as a predictive feature of MSC immunosuppressive function.

Category: Journal Article
PubMed ID: #28283659 DOI: 10.1073/pnas.1617933114
PubMed Central ID: #PMC5380055
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2016-09-21 Entry Last Modified: 2019-06-09