Evaluation of various bioreactor process systems for the production of induced pluripotent stem cells

Abstract

Induced pluripotent stem cells (iPSCs) bear potential to change the paradigms of conventional medicine. However, producing sufficient numbers of pluripotent and homogenous iPSC for therapeutic applications is challenging, in particular when using standard adherent cell culture. Suspension systems are prone to automation and thus represent a suitable alternative. Moreover, several well-established suspension culture vessels are already available. To support decision-making when establishing a cell production process, different culture systems were compared regarding the ability to standardize, product quality, economic efficiency, and potential for process optimization. Standard adherent culture was considered as a reference. In all experiments, the previously published AR1034ZIMA human iPSC line (ARiPS) was used. Culture systems comprised simple devices such as Petri dishes, Erlenmeyer flaks, as well as a computationally modelled and optimized stirred bioreactor. Highest standardization and cell yield was achieved when using the stirred bioreactor system, whereas Erlenmeyer flasks provided a good economic efficiency. Cell quality was comparable for all investigated vessels. Results indicate that the culture system should be carefully selected according to the application-specific requirements. Further, we show that low-cost culture vessels facilitate the production of high cell yields exhibiting a reasonable cell quality. Graphical abstract Introduction