Morphological profiling using machine learning reveals emergent subpopulations of interferon-γ-stimulated mesenchymal stromal cells that predict immunosuppression.

Journal: Cytotherapy
PMID: 30503100

Abstract

BACKGROUND: Although a preponderance of pre-clinical data demonstrates the immunosuppressive potential of mesenchymal stromal cells (MSCs), significant heterogeneity and lack of critical quality attributes (CQAs) based on immunosuppressive capacity likely have contributed to inconsistent clinical outcomes. This heterogeneity exists not only between MSC lots derived from different donors, tissues and manufacturing conditions, but also within a given MSC lot in the form of functional subpopulations. We therefore explored the potential of functionally relevant morphological profiling (FRMP) to identify morphological subpopulations predictive of the immunosuppressive capacity of MSCs derived from multiple donors, manufacturers and passages.

Authors

  • Ross A Marklein
    Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA; School of Chemical, Materials, and Biomedical Engineering, University of Georgia, Athens, Georgia, USA. Electronic address: ross.marklein@uga.edu.
  • Matthew W Klinker
    Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
  • Katherine A Drake
    Cytobank, Inc., Mountain View, California, USA.
  • Hannah G Polikowsky
    Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN.
  • Elizabeth C Lessey-Morillon
    Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.
  • Steven R Bauer
    Division of Cellular and Gene Therapies, Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA. Electronic address: steven.bauer@fda.hhs.gov.

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