Centre for Biochemical Engineering and Cell Cultivation Techniques, Institute of Chemistry and Biotechnology, Zurich University of Applied Sciences, Grüentalstrasse 14, 8820, Wädenswil, Switzerland.
Mares Advanced Therapies, 48268, Greven, Germany.
Appl Microbiol Biotechnol. 2023 Jul;107(14):4429-4445. doi: 10.1007/s00253-023-12583-4. Epub 2023 May 29.
Stem cell-based cell therapeutics and especially those based on human mesenchymal stem cells (hMSCs) and induced pluripotent stem cells (hiPSCs) are said to have enormous developmental potential in the coming years. Their applications range from the treatment of orthopedic disorders and cardiovascular diseases to autoimmune diseases and even cancer. However, while more than 27 hMSC-derived therapeutics are currently commercially available, hiPSC-based therapeutics have yet to complete the regulatory approval process. Based on a review of the current commercially available hMSC-derived therapeutic products and upcoming hiPSC-derived products in phase 2 and 3, this paper compares the cell therapy manufacturing process between these two cell types. Moreover, the similarities as well as differences are highlighted and the resulting impact on the production process discussed. Here, emphasis is placed on (i) hMSC and hiPSC characteristics, safety, and ethical aspects, (ii) their morphology and process requirements, as well as (iii) their 2- and 3-dimensional cultivations in dependence of the applied culture medium and process mode. In doing so, also downstream processing aspects are covered and the role of single-use technology is discussed. KEY POINTS: • Mesenchymal and induced pluripotent stem cells exhibit distinct behaviors during cultivation • Single-use stirred bioreactor systems are preferred for the cultivation of both cell types • Future research should adapt and modify downstream processes to available single-use devices.
基于干细胞的细胞治疗，特别是基于人骨髓间充质干细胞（hMSC）和诱导多能干细胞（hiPSC）的细胞治疗，在未来几年内具有巨大的发展潜力。它们的应用范围从骨科疾病和心血管疾病的治疗到自身免疫性疾病，甚至癌症。然而，尽管目前已有超过 27 种 hMSC 衍生的治疗方法可商业化应用，但 hiPSC 衍生的治疗方法尚未完成监管批准程序。本文基于对当前市售 hMSC 衍生治疗产品和即将进入 2 期和 3 期临床试验的 hiPSC 衍生产品的回顾，比较了这两种细胞类型的细胞治疗制造工艺。此外，还强调了它们之间的相似之处和不同之处，并讨论了对生产工艺的影响。这里重点介绍了：（i）hMSC 和 hiPSC 的特性、安全性和伦理方面，（ii）它们的形态和工艺要求，以及（iii）它们在应用的培养基和工艺模式下的 2 维和 3 维培养。在这样做的过程中，还涵盖了下游处理方面，并讨论了一次性使用技术的作用。要点：• 在培养过程中，间充质干细胞和诱导多能干细胞表现出不同的行为• 一次性搅拌生物反应器系统是这两种细胞类型培养的首选• 未来的研究应适应和修改下游工艺，以适应现有的一次性使用设备。
