Rendra Erika, Scaccia Eleonora, Bieback Karen
Institute of Transfusion Medicine and Immunology, Mannheim Institute of Innate Immunoscience, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
FlowCore Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, 68167, Germany.
F1000Res. 2020 Feb 27;9. doi: 10.12688/f1000research.21862.1. eCollection 2020.
Mesenchymal stromal cells (MSCs) are among of the most studied cell type for cellular therapy thanks to the ease of isolation, cultivation, and the high expansion potential. In 2018, the European Medicines Agency finally granted the first marketing authorization for an MSC product. Despite the numerous promising results in preclinical studies, translation into routine practice still lags behind: therapeutic benefits of MSCs are not as satisfactory in clinical trial settings as they appear to be in preclinical models. The bench-to-bedside-and-back approach and careful evaluation of discrepancies between preclinical and clinical results have provided valuable insights into critical components of MSC manufacturing, their mechanisms of action, and how to evaluate and quality-control them. We sum up these past developments in the introductory section ("Mesenchymal stromal cells: name follows function"). From the huge amount of information, we then selected a few examples to illustrate challenges and opportunities to improve MSCs for clinical purposes. These include tissue origin of MSCs, MSC culture conditions, immune compatibility, and route of application and dosing. Finally, we add some information on MSC mechanisms of action and translation into potency assays and give an outlook on future perspectives raising the question of whether the future clinical product may be cell-based or cell-derived.
间充质基质细胞(MSCs)因其易于分离、培养且具有高扩增潜力,是细胞治疗领域研究最多的细胞类型之一。2018年,欧洲药品管理局最终批准了首个间充质基质细胞产品的上市许可。尽管临床前研究取得了众多令人鼓舞的结果,但向常规临床实践的转化仍滞后:间充质基质细胞的治疗益处在临床试验环境中并不像在临床前模型中那样令人满意。从实验台到病床再回到实验台的方法以及对临床前和临床结果差异的仔细评估,为间充质基质细胞制造的关键组成部分、其作用机制以及如何评估和质量控制提供了宝贵的见解。我们在引言部分(“间充质基质细胞:名随功能”)总结了这些过去的进展。然后,从大量信息中,我们选择了几个例子来说明为临床目的改进间充质基质细胞所面临的挑战和机遇。这些包括间充质基质细胞的组织来源、间充质基质细胞培养条件、免疫相容性以及应用途径和剂量。最后,我们补充了一些关于间充质基质细胞作用机制以及转化为效力测定的信息,并对未来前景进行了展望,提出了未来临床产品可能是基于细胞还是细胞衍生的问题。