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

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.

List of scientific papers

I. Sara Padrell Sánchez*, Sandra Petrus-Reurer*, Pankaj Kumar*, Monica Aronsson, Helder André, Hammurabi Bartuma, Alvaro Plaza Reyes, Emeline F. Nandrot, Anders Kvanta, Fredrik Lanner. Preclinical safety studies of human embryonic stem cell-derived retinal pigment epithelial cells for the treatment of age-related macular degeneration. Stem Cells Translational Medicine. *These authors contributed equally to this work. [Submitted]

II. Alvaro Plaza Reyes*, Sandra Petrus-Reurer*, Sara Padrell Sánchez, Pankaj Kumar, Iyadh Douagi, Hammurabi Bartuma, Monica Aronsson, Sofie Westman, Emma Lardner, Helder André, Anna Falk, Emeline F. Nandrot, Anders Kvanta, Fredrik Lanner. Identification of cell surface markers and establishment of monolayer differentiation to retinal pigment epithelial cells. *These authors contributed equally to this work. [Accepted]
https://doi.org/10.1038/s41467-020-15326-5

III. Sara Padrell Sánchez, Heather Main, Mona Hedenskog, Fredrik Lanner. Establishment of GMP-compatible production of hESC-derived RPE cells. [Manuscript]

IV. Marc Parrilla, María Cuartero, Sara Padrell Sánchez, Mina Rajabi, Niclas Roxhed, Frank Niklaus, and Gastón A. Crespo. Wearable All-Solid-State Potentiometric Microneedle Patch for Intradermal Potassium Detection. Analytical Chemistry. 2019, 91, 1578-1586.
https://doi.org/10.1021/acs.analchem.8b04877

V. Rocío Cánovas, Sara Padrell Sánchez, Marc Parrilla, María Cuartero, and Gastón A. Crespo. Cytotoxicity Study of Ionophore-Based Membranes: Toward On-Body and in Vivo Ion Sensing. ACS Sens. 2019, 4, 2524-2535.
https://doi.org/10.1021/acssensors.9b01322