Scalable, safe and GMP-compatible production of embryonic stem cell derived retinal pigment epithelial cells

Sammanfattning: Regenerative medicine is an exponentially growing field that aims to regenerate a lost function, cell type or tissue due to damage, ageing or disease. Currently, more than 30,000 gene- and cell-based therapies have been or are being tested in clinical trials. Since the eye benefits from accessibility and a supposed to be immune privilege, many groups are exploring different strategies to treat diseases affecting this organ. Age-related macular degeneration (AMD), the leading cause of blindness in people aged over 65 years old, could be one of the first diseases treated with human pluripotent stem cells (hPSC)- derived therapies. This thesis has been focused on the development of a scalable, robust, defined and xeno-free protocol to differentiate hPSC into RPE-like cells, ensuring the safety of the obtained product through genomic, tumorigenicity and biodistribution studies. Finally, the differentiation of an in-house derived GMP-grade hESC line using a completely GMPcompliant protocol, together with the validation of a set of in-process and Quality Control tests has allowed to engage in conversations with the regulatory authorities to bring these cells closer to near clinical trials, and ultimately to AMD patients.