Impact of microcarrier concentration on mesenchymal stem cell growth and death: Experiments and modeling

Abstract

Mesenchymal stem cell (MSC) products are promising therapeutic candidates to treat a wide range of pathologies. The successful commercialization of these cell therapies will, however, depend on the development of reproducible cell production processes. For this, using microcarriers as growth supports within controlled conditions may be a viable process option. Although increasing microcarrier concentration may be associated with greater productivity due to the increased available culture surface, additional friction or shocks between microcarriers are likely to lead to undesired cell death. However, data detailing the impact of microcarrier collisions on MSC growth remains scarce. The following work demonstrates that MSC growth on microcarriers is greatly influenced by particle concentration even when little impact is observed on the apparent growth rate. It is suggested that the apparent growth rate may result in an equilibrium between growth and death kinetics which are independently affected by particle concentration and that certain MSC quality attributes may be progressively degraded in parallel. In addition, the theoretical reduction of the MSC growth rate was modeled according to the ratio between the average interparticle distance and the Kolmogorov scale. This study is an original contribution toward understanding the hydrodynamic effects in microcarrier‐based stem cell cultures.

Seed Train Optimization in Microcarrier-Based Cell Culture Post In Situ Cell Detachment through Scale-Down Hybrid Modeling

“…They explored an MC concentration range of 2 to 5 g/L and found no significant difference in achievable maximum cell concentration between 4 and 5 g/L of Cytodex 1 [ 49 ]. Moreover, higher MC concentrations were associated with increased occurrences of bead-to-bead collision and bead-to-reactor parts collision, posing a potential risk of damage to the cells [ 53 , 54 ]. Nienow et al (2013) explained that the potential damage due to bead-to-bead collision and bead-to-impeller collision is proportional to MC concentration with the power of 1 and 2, respectively [ 55 ].…”