de Wolf Charlotte, van de Bovenkamp Marja, Hoefnagel Marcel
Medicines Evaluation Board (CBG-MEB), Utrecht, The Netherlands.
Medicines Evaluation Board (CBG-MEB), Utrecht, The Netherlands.
Cytotherapy. 2017 Jul;19(7):784-797. doi: 10.1016/j.jcyt.2017.03.076. Epub 2017 Apr 27.
Mesenchymal stromal cells (MSCs) are multipotent cells derived from various tissues that can differentiate into several cell types. MSCs are able to modulate the response of immune cells of the innate and adaptive immune system. Because of these multimodal properties, the potential use of MSCs for immunotherapies is currently explored in various clinical indications. Due to the diversity of potential MSC medicinal products at the level of cell source, manufacturing process and indication, distinct functionality tests may be needed to ensure the quality for each of the different products. In this review, we focus on in vitro potency assays proposed for characterization and release of different MSC medicinal products. We discuss the most used functional assays, as presented in scientific advices and literature, highlighting specific advantages and limitations of the various assays. Currently, the most proposed and accepted potency assay for release is based on in vitro inhibition of T cell proliferation or other functionalities. However, for some products, assays based on other MSC or responder cell properties may be more appropriate. In all cases, the biological relevance of the proposed assay for the intended clinical activity should be substantiated with appropriate product-specific (non-)clinical data. In case practical considerations prevent the use of the ideal potency assay at release, use of a surrogate marker or test could be considered if correlation with functionality has been demonstrated. Nevertheless, as the field of MSC immunology is evolving, improvements can be expected in relevant assays and consequently in guidance related to potency testing.
间充质基质细胞（MSCs）是源自各种组织的多能细胞，能够分化为多种细胞类型。MSCs能够调节先天性和适应性免疫系统免疫细胞的反应。由于这些多模态特性，目前正在各种临床适应症中探索MSCs用于免疫治疗的潜在用途。由于潜在的MSCs药用产品在细胞来源、生产工艺和适应症层面存在多样性，可能需要不同的功能测试来确保每种不同产品的质量。在本综述中，我们重点关注为不同MSCs药用产品的表征和放行提出的体外效力测定方法。我们讨论了科学建议和文献中介绍的最常用的功能测定方法，突出了各种测定方法的具体优点和局限性。目前，最常被提议和接受的放行效力测定方法是基于体外抑制T细胞增殖或其他功能。然而，对于某些产品，基于其他MSCs或反应细胞特性的测定方法可能更合适。在所有情况下，所提议的测定方法与预期临床活性的生物学相关性都应以适当的产品特异性（非）临床数据来证实。如果实际考虑因素妨碍在放行时使用理想的效力测定方法，那么如果已证明与功能具有相关性，则可以考虑使用替代标志物或测试。尽管如此，随着MSCs免疫学领域的不断发展，预计相关测定方法以及效力测试指南都会有所改进。
