期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 114, 期 13, 页码 E2598-E2607出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1617933114
关键词
immunosuppression; mesenchymal stromal cells; morphology; high-content imaging; interferon-gamma
资金
- Food and Drug Administration Modernizing Science grant program
- Biomedical Advanced Research and Development Authority grant
- Medical Countermeasures Initiative
- Division of Cell and Gene Therapies
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-gamma stimulation significantly correlated with immunosuppressive capacity and accurately predicted the immunosuppressive capacity of MSC lines in a validation cohort. IFN-gamma enhanced the immunosuppressive capacity of all MSC lines, and morphology predicted the magnitude of IFN-gamma-enhanced immunosuppressive activity. Together, these data identify MSC morphology as a predictive feature of MSC immunosuppressive function.
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