Making 3D possible: large scale organoid expansion using bioprocess design


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Victoria Marsh Durban1,Mairian Thomas1,Kim Luetchford1,Trevor Dale1,Marianne Ellis1
1Cellesce Ltd

Abstract

Background

While it is increasingly understood 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 predictive ability in efficacy and toxicity assays, and therefore reducing and replacing the use of animal models early in the drug discovery pipeline. Organoids contain all of the key cell types of their tissue of origin: stem cells, allowing extended culture of structures; and differentiated cells, retaining physiologically relevant functions. Moreover, organoids can be grown from diseased tissues, retaining pathology and tumour heterogeneity, and exhibit tumour specific functions, such as cancer cell invasion. However, the production of organoids for use in medium-to-high throughput assays is currently highly time consuming and labour intensive, with batch-to-batch variation of organoids limiting assay reproducibility.

Method

Cellesce are currently developing 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 animal testing in early-stage drug discovery.

Results

We have expanded 10 human colorectal cancer organoid lines through culture in the proprietary CXP1 bioreactor, and all lines have been validated against a preliminary drug screen. Bioreactor-expanded organoids are comparable to organoids grown by traditional manual methods.

Conclusion

Standardised colorectal cancer organoids are produced in sufficient quantities to allow for drug screening in high throughput formats and to produce frozen batches that can be used ‘off the shelf’.