Bioprocess Engineering Strategies for Stem Cell-Based Therapies and Regenerative Medicine

Recent advances in the establishment of human embryonic, induced pluripotent and adult stem cell lines and the discovery of organ-specific stem cells with differentiation potential have substantially accelerated the potential of using these cells in regenerative medicine. Before any clinical application, stem cells need to be isolated, cultivated, differentiated into committed tissue precursor cells, stored and transported to the bed-side of a patient. The development of reliable in vitro systems for stem cell growth is a valuable tool to study the mechanisms controlling the expansion and differentiation of stem cells. Successful ex vivo models will enable the study of the dynamics and mechanisms of cell differentiation and organ development. The need for improved cultivation methods is also driven by the fact that most potential therapeutic applications are limited by the availability of stem cells or their derivatives. The in vitro propagation of stem cell populations remains undeveloped and is a major challenge because of the complex kinetics of the heterogeneous starting culture population, the transient nature of the subpopulations of interest and the complex interactions between the culture parameters. This lecture presents bioprocess concepts towards the ex vivo expansion and differentiation of stem cells in bioreactors, while maintaining their functional characteristics, including the ability to differentiate into appropriate receptive tissues. Adult mesenchymal and pluripotent stem cells and their differentiation in neural and cardiac stem cells in microcarrier-based culture systems are analysed.