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  • 标题:Morphological features of IFN-γ–stimulated mesenchymal stromal cells predict overall immunosuppressive capacity
  • 本地全文:下载
  • 作者:Matthew W. Klinker ; Ross A. Marklein ; Jessica L. Lo Surdo
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2017
  • 卷号:114
  • 期号:13
  • 页码:E2598-E2607
  • DOI:10.1073/pnas.1617933114
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要: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.
  • 关键词:immunosuppression ; mesenchymal stromal cells ; morphology ; high-content imaging ; interferon-gamma
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