ePoster

Clinical grade production of large-scale neural progenitor cells (NPC) for Huntington’s disease treatment

Josep M. Canals, Marc Estarellas, Georgina Bombau, Maria Camanyes, Irene Porcar, Jordi Abante, Unai Perpiña
FENS Forum 2024(2024)
Messe Wien Exhibition & Congress Center, Vienna, Austria

Conference

FENS Forum 2024

Messe Wien Exhibition & Congress Center, Vienna, Austria

Resources

Authors & Affiliations

Josep M. Canals, Marc Estarellas, Georgina Bombau, Maria Camanyes, Irene Porcar, Jordi Abante, Unai Perpiña

Abstract

Regenerative medicine aims to revolutionize medical practice by offering cures for severe diseases. This is achieved through the utilization of human pluripotent stem cell (hPSC) lines, which undergo controlled differentiation before being transplanted into patients. A significant challenge lies in developing safe, robust, and controlled differentiation protocols, requiring the adaptation of research-only reagents to good manufacturing practice (GMP) standards.Cell-based therapies for Huntington’s disease aspire to restore neuronal circuitry and function by replacing lost neurons. Here, we present a robust and reproducible GMP-compliant protocol for the maintenance and differentiation of hPSC into neural progenitor cells (NPC) suitable for clinical applications. We demonstrate the preservation of cell survival, morphology, pluripotent properties, and attachment rates of hESC throughout maintenance and scale-up steps. During the cryopreservation process, we demonstrate that using a controlled-rate freezer, as well as increasing feezed cell concentrations, enhances the cellular recovery rate. Upon differentiation, NPC exhibits the characteristic markers of Striatal Projection Neurons (SPNs) and demonstrate functionality upon maturation. Stringent quality controls, including mycoplasma, endotoxins, sterility, karyotype, microsatellites, flow cytometry and gene expression profile are systematically implemented in both instances to ascertain the effectiveness and safety of the therapeutic product. Overall, we report the feasibility of derivation and differentiation of clinical-grade hPSC lines into NPC under GMP-compliant conditions. Our protocols could be used as a flexible tool to speed up translation-to-clinic of hPSC for a variety of neurological therapies or regenerative medicine studies.

Unique ID: fens-24/clinical-grade-production-large-scale-f2ef4403