Human embryonic stem cell expansion and differentiation for clinical applications

Human embryonic stem cells hold great promises for the future of cell-based therapies and drug development in clinical applications. Understanding the complex cross-talk between stem cells and its environment, both spatially and temporally, is critical as it allows the creation of an optimal bioreactor for the controlled and regulated expansion of sufficient numbers of stem cells, followed by their differentiation towards the desired lineages. To create these optimal conditions for stem cell bioprocessing, considerations must be given to cell-cell signaling, and cell interactions with physical, mechanical and biochemical cues in its surrounding microenvironment. The ability to control and integrate stem cell expansion with differentiation in a bioreactor will determine the functionality, purity and quality of the resulting stem cells and its derivatives to meet the demands of clinical applications. This article highlights current progress in animal feeder-free cultures, serum free media, and three dimensional static and stirred cultures. Current limitations such as spontaneous differentiation, cell separation/purification and process monitoring will be considered. We predict that the application of tissue engineering principles and new techniques (such as the engineered niche, nanotechnology and biomaterials into the bioprocess design), could converge to overcome challenges such as uncontrolled stem cell differentiation in a stirred bioreactor. These novel approaches will propel bioprocess strategies to a new level, to ensure product quality and safety, advance the use of stem cells in cell-based therapy and drug development, resulting in improved clinical outcomes for the patients.

Duke Scholars

Author Seog Oh Physics