International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials.
International Society for Cellular Therapy perspective on immune functional assays for mesenchymal stromal cells as potency release criterion for advanced phase clinical trials.
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DOI：
10.1016/j.jcyt.2015.11.008
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发表时间：
2016-02
期刊：
影响因子：
4.5
通讯作者：
Sensebe L
中科院分区：
文献类型：
--
作者：
Galipeau J;Krampera M;Barrett J;Dazzi F;Deans RJ;DeBruijn J;Dominici M;Fibbe WE;Gee AP;Gimble JM;Hematti P;Koh MB;LeBlanc K;Martin I;McNiece IK;Mendicino M;Oh S;Ortiz L;Phinney DG;Planat V;Shi Y;Stroncek DF;Viswanathan S;Weiss DJ;Sensebe L
间充质间质细胞（MSCs）作为一种治疗以致病性自身免疫、同种免疫和炎症过程为特征的疾病的药物，目前在工业和学术资助的研究中涵盖了早期到晚期临床试验的范围。广泛的共识是，尽管不同的组织来源和不同的培养扩增方案，人类间质干细胞样细胞产品可能具有共同的基本作用机制，介导其抗炎和组织修复功能。鉴定效力的功能标记物，并将其减少到标准化，易于部署的测量方法的实践，将有利于该领域。这将满足机制研究和释放效价测定的开发，以满足监管机构进行高级临床研究及其最终注册的要求。为了满足这一未满足的需求，国际细胞治疗学会（ISCT）于2015年5月在拉斯维加斯举行的第21届ISCT年会的国际研讨会上讨论了这一问题。研讨会的范围集中在讨论与针对免疫疾病的临床适应症中msc样产品免疫调节相关的效价测定。我们在此提供本次论坛产生的共识观点。我们建议对选定的MSC标记物进行重点分析，并通过体外许可和测定矩阵进行量化，以响应监管机构的要求。研讨会参与者确定了三种可以为基质分析方法提供信息的首选分析方法：选定基因产物的定量RNA分析；功能相关表面标记物的流式细胞术分析及分泌组蛋白检测。我们还提倡以“开放获取”的方式，例如通过出版物或数据库收集，向公众提供监管机构可接受的效价测定。
Mesenchymal stromal cells (MSCs) as a pharmaceutical for ailments characterized by pathogenic autoimmune, alloimmune and inflammatory processes now cover the spectrum of early- to late-phase clinical trials in both industry and academic sponsored studies. There is a broad consensus that despite different tissue sourcing and varied culture expansion protocols, human MSC-like cell products likely share fundamental mechanisms of action mediating their anti-inflammatory and tissue repair functionalities. Identification of functional markers of potency and reduction to practice of standardized, easily deployable methods of measurements of such would benefit the field. This would satisfy both mechanistic research as well as development of release potency assays to meet Regulatory Authority requirements for conduct of advanced clinical studies and their eventual registration. In response to this unmet need, the International Society for Cellular Therapy (ISCT) addressed the issue at an international workshop in May 2015 as part of the 21st ISCT annual meeting in Las Vegas. The scope of the workshop was focused on discussing potency assays germane to immunomodulation by MSC-like products in clinical indications targeting immune disorders. We here provide consensus perspective arising from this forum. We propose that focused analysis of selected MSC markers robustly deployed by in vitro licensing and metricized with a matrix of assays should be responsive to requirements from Regulatory Authorities. Workshop participants identified three preferred analytic methods that could inform a matrix assay approach: quantitative RNA analysis of selected gene products; flow cytometry analysis of functionally relevant surface markers and protein-based assay of secretome. We also advocate that potency assays acceptable to the Regulatory Authorities be rendered publicly accessible in an “open-access” manner, such as through publication or database collection.