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

Cell Rep. 2018 Feb 27;22(9):2504-2517. doi: 10.1016/j.celrep.2018.02.013.

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.

Keywords: PBMCs; assay matrix; interferon-γ; mesenchymal stromal cells; secretome; transcriptome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication / drug effects
  • Cell Proliferation / drug effects
  • Coculture Techniques
  • Cytokines / metabolism
  • Humans
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / metabolism
  • Interferon-gamma / pharmacology
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / drug effects

Substances

  • Cytokines
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interferon-gamma