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Potency Analysis of Mesenchymal Stromal Cells Using a Combinatorial Assay Matrix Approach.
Cell Reports ( IF 7.5 ) Pub Date : 2018-Feb-27 , DOI: 10.1016/j.celrep.2018.02.013
Raghavan Chinnadurai 1 , Devi Rajan 2 , Muna Qayed 2 , Dalia Arafat 3 , Marco Garcia 4 , Yifei Liu 5 , Subra Kugathasan 2 , Larry J Anderson 2 , Greg Gibson 3 , Jacques Galipeau 1
Affiliation  

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.

中文翻译:


使用组合测定矩阵方法对间充质基质细胞进行效力分析。



需要确定能够表征 MSC 免疫效力的测定方法,以用于高级临床试验。间充质干细胞具有许多假定的再生和免疫调节特性,并且分析矩阵方法可能最好地捕获所涉及的效应通路。我们测试了两种测定系统来测量源自人类受试者的 MSC 的效力:MSC 分泌组分析和基于 RNA 的定量阵列,用于检测 MSC 免疫调节和归巢特性特异的基因。分泌组分析确定了一种独特的细胞因子特征,该特征在 MSC 中上调,在应答者 PBMC 中下调,并与 T 细胞抑制相关。使用干扰素-γ 作为活化 PBMC 对 MSC 作用的替代物,可以作为在效力测定中使用人 PBMC 作为应答细胞的替代方案。我们的方法和结果定义并简化了 MSC 的多功能或基质反应,并可作为稳健效力分析的平台。
更新日期:2018-02-28
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