Abstract

Making 3D Possible: Large-Scale Organoid Production Using Bioprocess Design

Victoria Marsh Durban, Lead Scientist, Cellesce Limited

While it is increasingly appreciated that 2D cell models poorly represent physiological drug responses, 3D alternatives have not yet replaced their widespread use. Organoid technology has the potential to transform drug discovery, improving the predictiveness of efficacy and toxicity assays, and therefore reducing the use of animal models in the drug discovery pipeline. Although organoid models are recognised as a superior in vitro tool, the production of organoids is currently a time consuming, highly manual process. Moreover, the small batch sizes achieved and substantial variability of manual batch production significantly limits the reproducibility of organoid-based assays. These issues preclude the use of organoids in the medium-to-high throughput formats required for early drug discovery. Cellesce has developed proprietary bioprocessing systems for the expansion of organoids at scale, with the long-term goal of positioning organoid technology as a cost-effective and accurate alternative to 2D cell models in drug discovery. Using our first-generation bioprocess, “CXP1”, we have successfully shown that breast and colorectal cancer-derived organoids grown in bioreactors are comparable to those grown according to traditional manual methods. Bioprocessed organoids are size standardised, produced in sufficient quantities to allow for drug screening in high-throughput formats, and are available in frozen format suitable for use ‘off the shelf’.