Year 2

We have developed GMP-compliant suspension cell culture processes for scalable production of human pluripotent stem cells (hPSCs) and derivatives. These processes have been invaluable in our support of CIRM- and NIH-funded regenerative medicine projects, including those with RPE, NSC, DA neurons and cardiomyocytes (CM), as well as for production of GMP banks of hPSC for various projects. Our GMP-compliant suspension culture CM production process has made pre-clinical animal studies and small early clinical trials practical. However, while the current CM system has been readily transferred to other groups and is meeting current production requirements, the scale requirements for anticipated high dose clinical trials is beyond the practical limitation of our spinner flask-based system. Our experience using bag-based bioreactors for non-hESC products suggested that scale-up in bags will be more controllable and predictable than spinners or stir-tanks reactors. It is also a readily transferred technology. We successfully adapted our suspension hPSC and CM processes to a bag system, and demonstrated scalability at a 3L scale generating highly pure batches of hPSC-derived CMs at the multibillion cell scale. Success in this project removes a key barrier to developing many regenerative medicine products, and in particular those where high human doses are anticipated, such as CM.