Strategies for bringing stem cell-derived dopamine neurons to the clinic

Concerted efforts are realizing cell-based therapy for Parkinson's disease (PD). In this chapter, I describe efforts at the Center for iPS Cell Research and Application (CiRA), Kyoto University. These efforts use induced pluripotent stem cells (iPSCs) as donor cells. The iPSCs were established as human leukocyte antigen homozygous at CiRA and are intended for allogeneic transplantation. Our manufacturing protocol includes a feeder-free cell culture with laminin fragment LM511-E8 and the sorting of CORIN+ cells. Animal experiments, including those with monkey PD models, proved that the grafted cells survive and function as dopaminergic neurons in the brain without forming any tumors. Furthermore, I emphasize that not only the donor cells but also the host brain environment is critical for successful transplantation. To achieve optimization of the host environment, drug administration, gene modification, and rehabilitation are recommended. Based on these results, researchers plan to start a clinical trial at Kyoto University Hospital in the near future.