PhD Candidate Karolinska Institutet Stockholm, Stockholms Lan, Sweden
Abstract: Manual handling in cell therapy production, particularly for adherent cell types, poses challenges for scalability and increases operator variability. The scarcity of specialized Good Manufacturing Practices (GMP) production facilities further limits the accessibility to future cell therapies. This study investigates the use of automated systems to streamline cell expansion, differentiation, and the formulation of cryopreserved cell products for clinical administration. We used the CliniMACS Prodigy system with external CellSTACK to derive Retinal Pigment Epithelium (RPE) cells from human embryonic stem cells (hESCs), utilizing a GMP-compatible protocol. Additionally, we employed an acoustic-based, automated cell trapping system (AcouTrap) for washing our final, cryopreserved cell product from their freezing medium. Our results show that cell morphology, viability and marker expression of cells cultured in the CliniMACS Prodigy system were comparable to cells cultured manually. PEDF secretion levels and Trans-Epithelial Electrical Resistance measurements (TEER) further confirm the functionality of our RPE cells derived from both processes. The AcouTrap system demonstrated efficient contaminant removal, with post-wash viability and functionality levels of the resulting RPE cells matching that of manually processed cells. The use of automated systems can efficiently increase cell therapy scalability, reproducibility and safety, while decreasing production cost and operator variation. Employing an automated cell washing system to prepare cryopreserved cell therapy products for patient administration can furthermore enable bedside formulation, thereby improving accessibility in regions lacking access to specialized GMP facilities.
