Numerical Methods for the Design and Description of In Vitro Expansion Processes of Human Mesenchymal Stem Cells
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-spe
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Numerical Methods for the Design and Description of In Vitro Expansion Processes of Human Mesenchymal Stem Cells Valentin Jossen, Dieter Eibl, and Regine Eibl
Contents 1 Introduction 2 In Vitro Expansion Approaches: Current Situation 2.1 Planar Approach (2D Cultures) 2.2 Dynamic Approach (3D Cultures) 3 Computational Fluid Dynamics as a Modern Tool for Bioreactor Characterization 3.1 Modelling Approaches 3.2 Advanced Fluid Flow Characterization of Small-Scale Spinner Flasks: A Case Study 4 Mathematical Growth Modelling of MC-Based hMSC Expansions 4.1 Modelling Approaches 4.2 Kinetic Growth Model for the MC-Based hMSC Expansion: A Case Study 5 Conclusions and Outlook References
Abstract 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
V. Jossen (*), D. Eibl, and R. Eibl Zurich University of Applied Sciences – Institute of Chemistry and Biotechnology, Wädenswil, Switzerland e-mail: [email protected]
V. Jossen et al.
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. Graphical Abstract
Keywords Computational Fluid Dynamics, Euler-Euler model, Euler-Lagrange model, Human mesenchymal stem cells, Kinetic growth modelling, Microcarrier technology, Single-use bioreactor
Abbreviations
CC CFD DMEM DSP
Collagen-coated Computational Fluid Dynamics Dulbecco’s Modified Eagle Medium Downstream processing
Numerical Methods for the Design and Description of In Vitro Expansion. . .
ECM bFGF FBS GMP hASC hBM-MSC hMSCs hPL HGF HSB LDA LES αMEM MC MCB MRF OTR PIV PS RB RMSD SIMPLE SM SU UCM USP VEGF VOF WCB
Extracellular matrix Basic fibroblast growth factor Fetal bovine serum Good manufacturing practice Human adipose tissue-derived stromal/s
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