Microgel Matrices for Human Cancer Organoid Production


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Jessica Pinheiro de Lucena-Thomas1,Kim Luetchford2,Marianne Ellis2,Paul De Bank1
1University of Bath,2Cellesce Ltd

Abstract

Background

Organoids are multicellular structures capable of mimicking tissue structure and tumour heterogeneity better than other available biological model systems. They are a powerful enabling technology in drug discovery because they can give more accurate test results, allow for high throughput screening, and also reduce the need of animal models. In order for organoids to be widely used in industrial and clinical applications, their robust production must be scaled up efficiently. Cellesce Ldt has developed a process to grow large numbers of organoids for commercial drug screening. The traditional manual culture and expansion of organoids is, however, labour intensive, expensive and heavily depend on expensive animal-derived matrix scaffolds, mainly Matrigel. These materials are expensive to produce and are prone to batch-to-batch variations. The aim of this study was to investigate non-animal derived polymers to reduce Matrigel use as 3D organoid matrix, focusing on the production of cell-containing hydrogel microbeads. 

Method

Material A and B, both derived hydrogel-forming biomaterials, were selected to form blends with Matrigel. The microbeads were produced by electrospraying and compared in terms of their physical properties. Finally, the ability of the cells to grow and form organoids within these blends was assessed and compared with the current method using Matrigel. 

Results

It was observed that material A-based blends were the only ones that supported organoid growth, with AM1 (1:1 material A:Matrigel ratio) being the optimum blend among the others.

Conclusion

This study concluded that the volume of Matrigel needed for growing organoids was reduced by 50%, thus providing a more sustainable and cost-effective means of organoid generation. The outcome of this research will be the basis for future bioreactor and scale-up studies.