Feasibility of manufacturing-scale bioproduction of novel next-generation 3D organoidcancer models in support of the Human Cancer Models Initiative


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Nirmal Perera, James Clinton, Penney McWilliams-Koeppen, Siddhartha Paul, Allison Ruchinskas, Dexhong Yin, Robert Newman

Abstract

Background

To meet the need for improved approaches to study cancer in vitro, there has been a surge in the development of novel research models utilizing advanced culture methods. These methods permit in vitro growth of cancer types previously not possible, and/or models with enhanced in vivo relevancy compared to traditional continuous cell lines. However, availability of these early-stage research models is currently limited and there is a lack of data on the ability to scale up production of these models to support the needs of the global research community.

Method

We cultured organoid models derived from human colon, pancreas, esophagus, and mammary tissues developed by laboratories contributing to the HCMI. Multiple unique donors were available for all tissues and both cancer and non-cancer models were available for two tissue types. Most models were maintained in culture continuously for at least 60 days (7-27 population doublings, > 10 passages). Tissue and donor variability was evident in model characteristics, including morphology (assessed by microscopy and immunocytochemistry), growth rate, and genetic stability (measured by short tandem repeats analysis).

Results

Of the target 10-15 models for the feasibility study, 16 were received in time for inclusion in the pilot phase feasibility study, 14 were cultured, and 12  completed all testing. Models provided were intended to be a representative selection of the 100 models to be produced during the pilot phase of the HCMI project.

Conclusion

While organoid culture represents a significant divergence from typical two-dimensional monolayer culture of continuous cell lines, our results show that these next-generation in vitro models are suitable for larger-scale bioproduction. 

Impact statement

This is vital to ensure the widespread availability of these models within the research community to facilitate applications like pre-clinical drug discovery and basic cancer research.