Date: 9th June 2020
Stem-cell-derived epithelial organoids are often used for the biological and biomedical modelling of tissues as they mimic many aspects of entire organs such as their properties and three-dimensional structures.
Whilst, they offer potential for personalised medicine and for improved screening of drugs, their use at an industrial scale has thus far been hampered. This is due to a lack of standardisation and quality control of the organoids in solid extracellular matrices, resulting in cells that grow in a disorderly fashion. This lack of homogeneity has meant that automated monitoring that is required in an industrial setting has not been achievable so far.
Now scientists from Switzerland have reported the fabrication of microengineered cell culture devices and scalable, automated methods for suspension culture, allowing the real-time analysis of thousands of individual gastrointestinal organoids trapped in microcavity arrays within a polymer-hydrogel substrate.
A soft lithography technique was used to mass-produce the gels whereby many tiny holes were imprinted into the gel. Each only a few micrometers in diameter, creating rows of U-shaped microwells. Each well then received about 100 cells (human or mouse intestinal cells), which clustered together and formed a relatively compact colony within about 30 minutes. The aggregated intestinal cells then grew and differentiated, producing functional intestinal organoids around 60 hours later. The soft hydrogel allowed the organoids to propagate uniformly, decreasing organoid heterogeneity.
The team used the devices to screen for anticancer drug candidates with patient-derived colorectal cancer organoids, and have applied high-content image-based phenotypic analyses to reveal insights into mechanisms of drug action.
The system is readily adaptable meaning that is can be used for a variety of organoids and is not restricted to the cancer field. The depth, the diameter and density of the microwells can readily be adapted as required.
It is hoped that this scalable organoid-culture technology will accelerate drug development and diagnostics. It should for the first time allow the mass production of standardised organoids. Indeed, two of the authors in the study have launched a start-up company, SUN Bioscience, to market the technology.
For more information please see the press release from EPFL
Brandenberg, N., S. Hoehnel, F. Kuttler, K. Homicsko, C. Ceroni, T. Ringel, N. Gjorevski, G. Schwank, G. Coukos, G. Turcatti and M. P. Lutolf (2020). “High-throughput automated organoid culture via stem-cell aggregation in microcavity arrays.” Nature Biomedical Engineering.