Zurich University of Applied Sciences - Institute of Chemistry and Biotechnology, Wädenswil, Switzerland.
Adv Biochem Eng Biotechnol. 2021;177:185-228. doi: 10.1007/10_2020_147.
Human mesenchymal stem cells (hMSCs) are a valuable source of cells for clinical applications (e.g., treatment of acute myocardial infarction or inflammatory diseases), especially in the field of regenerative medicine. However, for autologous (patient-specific) and allogeneic (off-the-shelf) hMSC-based therapies, in vitro expansion is necessary prior to the clinical application in order to achieve the required cell numbers. Safe, reproducible, and economic in vitro expansion of hMSCs for autologous and allogeneic therapies can be problematic because the cell material is restricted and the cells are sensitive to environmental changes. It is beneficial to collect detailed information on the hydrodynamic conditions and cell growth behavior in a bioreactor system, in order to develop a so called "Digital Twin" of the cultivation system and expansion process. Numerical methods, such as Computational Fluid Dynamics (CFD) which has become widely used in the biotech industry for studying local characteristics within bioreactors or kinetic growth modelling, provide possible solutions for such tasks.In this review, we will present the current state-of-the-art for the in vitro expansion of hMSCs. Different numerical tools, including numerical fluid flow simulations and cell growth modelling approaches for hMSCs, will be presented. In addition, a case study demonstrating the applicability of CFD and kinetic growth modelling for the development of an microcarrier-based hMSC process will be shown.
人骨髓间充质干细胞（hMSCs）是临床应用（例如，急性心肌梗死或炎症性疾病的治疗）的宝贵细胞来源，特别是在再生医学领域。然而，对于自体（患者特异性）和同种异体（现成）基于 hMSC 的治疗，在临床应用之前需要进行体外扩增，以达到所需的细胞数量。安全、可重复和经济的自体和同种异体 hMSC 体外扩增可能会出现问题，因为细胞材料受到限制，并且细胞对环境变化敏感。收集关于生物反应器系统中流体动力学条件和细胞生长行为的详细信息是有益的，以便开发培养系统和扩增过程的所谓“数字孪生体”。数值方法，如计算流体动力学（CFD），已在生物技术行业中广泛用于研究生物反应器内的局部特征或动力学生长建模，为这些任务提供了可能的解决方案。在这篇综述中，我们将介绍 hMSC 体外扩增的最新技术。将介绍不同的数值工具，包括用于 hMSCs 的数值流体流动模拟和细胞生长建模方法。此外，还将展示一个案例研究，展示 CFD 和动力学生长建模在开发基于微载体的 hMSC 工艺中的适用性。
