Biomanufacturing human pluripotent stem cells for therapeutic applications

Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs) can be propagated indefinitely and have the potential to differentiate to all cell types of the body. In addition, patient-specific human iPSCs and hESCs containing point mutations in genes that cause disease can be used to study diseases that have no adequate human in vitro or animal models. Harnessing the potential of these cells holds promise for future applications in cell therapy and regenerative medicine. Common methods of expanding and differentiating human pluripotent stem cells (hPSCs), including hESC and iPSC, require serum, mouse or human feeder cells, or feeder-conditioned medium. These methods are labor intensive and hard to scale, and sources of variability including growth factor fluctuations during preparation and culture complicate large-scale hPSC bioprocesses. Biomanufacturing cells from hPSCs requires development of fully defined, xeno-free culture medium and substrates formulated with human-derived, human recombinant proteins or chemically synthetic substrates under cGMP and improved processes for monitoring cell status and genomic stability during expansion and differentiation. In addition, robust and scalable differentiation methods must be developed. This chapter discusses recent progress and remaining challenges facing production of hPSC-derived cells.