Adv Biochem Eng Biotechnol (2021) 177: 185–228
https://doi.org/10.1007/10_2020_147
© Springer Nature Switzerland AG 2020
Published online: 23 October 2020
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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
2 In Vitro Expansion Approaches: Current Situation . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. . . . . . . . 191
2.1 Planar Approach (2D Cultures) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
2.2 Dynamic Approach (3D Cultures) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
3 Computational Fluid Dynamics as a Modern Tool for Bioreactor Characterization . . . . . . 200
3.1 Modelling Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
3.2 Advanced Fluid Flow Characterization of Small-Scale Spinner Flasks: A Case
Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
4 Mathematical Growth Modelling of MC-Based hMSC Expansions . . . . . . . . . . . . . . . . . . . . . . . 216
4.1 Modelling Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216
4.2 Kinetic Growth Model for the MC-Based hMSC Expansion: A Case Study . . . . . . . 217
5 Conclusions and Outlook . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . 221
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
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: valentin.jossen@zhaw.ch
https://doi.org/10.1007/10_2020_147
© Springer Nature Switzerland AG 2020
Published online: 23 October 2020
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 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
2 In Vitro Expansion Approaches: Current Situation . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. . . . . . . . 191
2.1 Planar Approach (2D Cultures) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
2.2 Dynamic Approach (3D Cultures) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
3 Computational Fluid Dynamics as a Modern Tool for Bioreactor Characterization . . . . . . 200
3.1 Modelling Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201
3.2 Advanced Fluid Flow Characterization of Small-Scale Spinner Flasks: A Case
Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
4 Mathematical Growth Modelling of MC-Based hMSC Expansions . . . . . . . . . . . . . . . . . . . . . . . 216
4.1 Modelling Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 216
4.2 Kinetic Growth Model for the MC-Based hMSC Expansion: A Case Study . . . . . . . 217
5 Conclusions and Outlook . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . 221
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 222
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: valentin.jossen@zhaw.ch