Kinetic modeling of human induced pluripotent stem cell expansion in suspension culture.

To date, practical application of mathematical models for model-based design of stem cell expansion processes is limited. Nevertheless, the first attempts show vast potential of this approach for the improvement of expansion process performance. This article presents the developed dynamic kinetic model of the human induced pluripotent stem cell expansion process in suspension culture. The model predicts cell growth, consumption of glucose and production of lactic acid, as well as the average aggregate size. The latter process variable is of particular importance for achieving high cell density. By adding botulinum hemagglutinin, an E-cadherin inhibitor and subsequent aggregate break-up, one can significantly increase performance of cell expansion process. After defining the appropriate optimization criteria and additional modification of the model, the latter can be further applied for model-based optimization of the final cell concentration by calculating optimal aggregate break-up and glucose/glutamine feeding strategies.