Potency Analysis of Mesenchymal Stromal Cells Using a Combinatorial Assay Matrix Approach.
Potency Analysis of Mesenchymal Stromal Cells Using a Combinatorial Assay Matrix Approach.
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DOI：
10.1016/j.celrep.2018.02.013
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发表时间：
2018-02-27
期刊：
影响因子：
8.8
通讯作者：
Galipeau J
中科院分区：
文献类型：
--
作者：
Chinnadurai R;Rajan D;Qayed M;Arafat D;Garcia M;Liu Y;Kugathasan S;Anderson LJ;Gibson G;Galipeau J
可以表征MSC免疫效力的测定需要被鉴定用于高级临床试验。间充质干细胞具有许多推定的再生和免疫调节特性，测定基质方法可以最好地捕获涉及的效应途径。我们已经测试了两种测定系统来测量来自人类受试者的MSC的效力：MSC分泌组分析和针对MSC的免疫调节和归巢特性的基因的基于定量RNA的阵列。分泌组分析鉴定了一种独特的细胞因子特征，其由MSC上调或在应答者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，作为在效价测定中使用人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，并可作为强大的效价分析平台。需要在先进的临床试验中定义间充质基质细胞（MSC）免疫效力的检测方法。Chinnadurai等人测试了结合分子遗传学和分泌组分析的体外测定矩阵方法，其元素可用于定义MSC免疫调节效力。
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.
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