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

• Type of Material: Article
• Authors: Raghavan Chinnadurai, University of Wisconsin; Devi Rajan, Emory University; Muna Qayed, Emory University; Dalia Arafat, Georgia Institute of Technology; Marco Garcia, Emory Healthcare; Yifei Liu, University of Wisconsin; Subra Kugathasan, Emory University; Larry J Anderson, Emory University; Greg Gibson, Georgia Institute of Technology; Jacques Galipeau, University of Wisconsin
• Language: English
• Date: 2018-02-27
• Publisher: Elsevier (Cell Press): OAJ
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors
• Final Published Version (URL): http://dx.doi.org/10.1016/j.celrep.2018.02.013
• Title of Journal or Parent Work: Cell Reports
• ISSN: 2211-1247
• Volume: 22
• Issue: 9
• Start Page: 2504
• End Page: 2517
• Grant/Funding Information: 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 directly supported by NIH/NIDDK award R01DK109508.; This work was also supported in part by the National Center for Advancing Translational Sciences of the NIH (UL1TR000454 and KL2TR000455 to M.Q.).
• Keywords: PERSPECTIVE; SUPPRESSION; CRYOPRESERVATION; STEM/STROMAL CELLS; THERAPY; INFLAMMATION; Life Sciences & Biomedicine; MODEL; CLINICAL-TRIALS; STEM-CELLS; INTERNATIONAL-SOCIETY; Science & Technology; Cell Biology
• Research Categories: Biology, Cell; Health Sciences, Medicine and Surgery; Health Sciences, General

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.