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Author Notes:

Correspondence: jgalipeau@wisc.edu.

R.C. designed the research plan, performed most experiments, analyzed results, and wrote the manuscript.

D.R. and L.J.A. helped with the cytokine multiplex experiments.

M.G. helped with MSC preparations.

S.K. and M.Q. provided bone marrow aspirates from patients with Crohn’s disease and GvHD, respectively.

D.A. and G.G. helped with the qPCR array.

Y.L. helped with statistical analysis.

J.G. designed the research plan, analyzed results, and wrote the manuscript.

We thank Shala Yuan for technical assistance.

The authors declare no competing interests.

Subjects:

Research Funding:

The study was supported by a grant from ACTSI/Immunoengineering Pilot Award (to G.G. and J.G.) and developmental funds from the Winship Cancer Institute of Emory University (to R.C.).

This work was also supported in part by the National Center for Advancing Translational Sciences of the NIH (UL1TR000454 and KL2TR000455 to M.Q.).

This work was directly supported by NIH/NIDDK award R01DK109508.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • STEM/STROMAL CELLS
  • STEM-CELLS
  • INTERNATIONAL-SOCIETY
  • CLINICAL-TRIALS
  • SUPPRESSION
  • THERAPY
  • INFLAMMATION
  • PERSPECTIVE
  • MODEL
  • CRYOPRESERVATION

Potency Analysis of Mesenchymal Stromal Cells Using a Combinatorial Assay Matrix Approach

Tools:

Journal Title:

Cell Reports

Volume:

Volume 22, Number 9

Publisher:

, Pages 2504-2517

Type of Work:

Article | Final Publisher PDF

Abstract:

Assays that can characterize MSC immune potency need to be identified for use in advanced clinical trials. MSCs possess a number of putative regenerative and immunomodulatory properties, and an assay matrix approach may best capture involved effector pathways. We have tested two assay systems to measure the potency of MSCs derived from human subjects: MSC secretome analysis and a quantitative RNA-based array for genes specific to immunomodulatory and homing properties of MSCs. Secretome analysis identified a unique cytokine signature that is upregulated by MSCs or downregulated in responder PBMCs and correlated with T cell suppression. Use of interferon-γ as a surrogate for the action of activated PBMCs on MSCs served as an alternative for the use of human PBMCs as responder cells in a potency assay. Our approach and results define and simplify the multifunctional or matrix responses of MSCs and may serve as a platform for robust potency analysis. Assays that inform on mesenchymal stromal cell (MSC) immune potency need to be defined in advanced clinical trials. Chinnadurai et al. tested an in vitro assay matrix approach combining molecular genetic and secretome analysis, elements of which could be deployed to define MSC immune modulatory potency.

Copyright information:

© 2018 The Authors

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