Department of Medicine, University of Wisconsin Carbone Comprehensive Cancer Center, University of Wisconsin - Madison, Madison, WI 53705, USA.
Department of Pediatrics, Children's Healthcare of Atlanta, Emory University, Atlanta, GA 30322, USA.
Cell Rep. 2018 Feb 27;22(9):2504-2517. doi: 10.1016/j.celrep.2018.02.013.
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.
需要鉴定能够描述 MSC 免疫效力的检测方法，以便用于高级临床试验。MSC 具有许多潜在的再生和免疫调节特性，而检测方法矩阵方法可能最能捕获相关的效应途径。我们已经测试了两种检测系统来测量源自人类供体的 MSC 的效力：MSC 分泌组分析和基于定量 RNA 的 MSC 免疫调节和归巢特性相关基因的阵列。分泌组分析鉴定出一种独特的细胞因子特征，该特征可被 MSC 上调或在反应性 PBMC 中下调，并与 T 细胞抑制相关。使用干扰素-γ作为激活的 PBMC 对 MSC 作用的替代物，可替代使用人 PBMC 作为效力检测中的反应细胞。我们的方法和结果定义并简化了 MSC 的多功能或基质反应，可作为强大效力分析的平台。
