French Anna, Bravery Christopher, Smith James, Chandra Amit, Archibald Peter, Gold Joseph D, Artzi Natalie, Kim Hae-Won, Barker Richard W, Meissner Alexander, Wu Joseph C, Knowles Jonathan C, Williams David, García-Cardeña Guillermo, Sipp Doug, Oh Steve, Loring Jeanne F, Rao Mahendra S, Reeve Brock, Wall Ivan, Carr Andrew J, Bure Kim, Stacey Glyn, Karp Jeffrey M, Snyder Evan Y, Brindley David A
Oxford-UCL Centre for the Advancement of Sustainable Medical Innovation and
Consulting on Advanced Biologicals Ltd., London, United Kingdom;
Stem Cells Transl Med. 2015 Mar;4(3):217-23. doi: 10.5966/sctm.2014-0233. Epub 2015 Feb 3.
There is a need for physical standards (reference materials) to ensure both reproducibility and consistency in the production of somatic cell types from human pluripotent stem cell (hPSC) sources. We have outlined the need for reference materials (RMs) in relation to the unique properties and concerns surrounding hPSC-derived products and suggest in-house approaches to RM generation relevant to basic research, drug screening, and therapeutic applications. hPSCs have an unparalleled potential as a source of somatic cells for drug screening, disease modeling, and therapeutic application. Undefined variation and product variability after differentiation to the lineage or cell type of interest impede efficient translation and can obscure the evaluation of clinical safety and efficacy. Moreover, in the absence of a consistent population, data generated from in vitro studies could be unreliable and irreproducible. Efforts to devise approaches and tools that facilitate improved consistency of hPSC-derived products, both as development tools and therapeutic products, will aid translation. Standards exist in both written and physical form; however, because many unknown factors persist in the field, premature written standards could inhibit rather than promote innovation and translation. We focused on the derivation of physical standard RMs. We outline the need for RMs and assess the approaches to in-house RM generation for hPSC-derived products, a critical tool for the analysis and control of product variation that can be applied by researchers and developers. We then explore potential routes for the generation of RMs, including both cellular and noncellular materials and novel methods that might provide valuable tools to measure and account for variation. Multiparametric techniques to identify "signatures" for therapeutically relevant cell types, such as neurons and cardiomyocytes that can be derived from hPSCs, would be of significant utility, although physical RMs will be required for clinical purposes.
需要物理标准（参考材料）来确保从人多能干细胞（hPSC）来源生产体细胞类型时的可重复性和一致性。我们概述了与hPSC衍生产品的独特性质和相关问题有关的参考材料（RM）的需求，并提出了与基础研究、药物筛选和治疗应用相关的RM生成的内部方法。hPSC作为药物筛选、疾病建模和治疗应用的体细胞来源具有无与伦比的潜力。分化为感兴趣的谱系或细胞类型后未定义的变异和产品变异性阻碍了有效转化，并可能掩盖临床安全性和疗效的评估。此外，在缺乏一致群体的情况下，体外研究产生的数据可能不可靠且不可重复。设计有助于提高hPSC衍生产品一致性的方法和工具，无论是作为开发工具还是治疗产品，都将有助于转化。标准以书面和物理形式存在；然而，由于该领域仍存在许多未知因素，过早的书面标准可能会抑制而不是促进创新和转化。我们专注于物理标准RM的推导。我们概述了RM的需求，并评估了hPSC衍生产品内部RM生成的方法，这是分析和控制产品变异的关键工具，可供研究人员和开发人员使用。然后，我们探索了RM生成的潜在途径，包括细胞和非细胞材料以及可能提供有价值工具来测量和解释变异的新方法。尽管临床应用需要物理RM，但多参数技术来识别治疗相关细胞类型（如可从hPSC衍生的神经元和心肌细胞）的“特征”将具有重要用途。
