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Cancer Models Forum

Posted by Henrietta, October 2020

Key takeaways from 'Combining  HUB  Organoids with Organ-on-a-Chip Technology: the Best of Two Worlds' webinar

On Tuesday 13th October, we tuned into the ‘Combining HUB Organoids with Organ-on-a-Chip Technology: the Best of Two Worlds’ webinar, hosted by MIMETAS in partnership with the Hubrecht Institute. The webinar covered the many exciting benefits and opportunities that organoids provide as a disease modelling technique, as well as how organoids can be combined with organ-on-a-chip technology to create a dual model with unique capabilities.

The development of HUB organoids in Hans Clevers lab at the Hubrecht Institute was centred on the idea that developing models which can more accurately mimic human biology in situ should help to enable more accurate translation from preclinical oncology studies to clinical trials. More than half of cancer patients today still have a very poor disease prognosis, and with cancer drugs currently holding a 95% failure rate from preclinical to clinical studies, there is a desperate need to improve the accuracy of early drug discovery to enable greater success further down the cancer drug pipeline. In the case of HUB organoids specifically, their development began with the fundamental study of LGR5+ epithelial stem cells in the intestine, both in terms of their normal functioning as well as how they develop in cancer, and these cells were subsequently expanded to create new model organoid systems. The aim of developing these models was threefold, namely:

  • To accurately capture patient and tumour heterogeneity
  • To be genetically and phenotypically stable over a long period of time
  • To mimic clinical patient responses

Since their initial development, the HUB organoids have been used across a number of different applications, including for early stage disease characterisation, preclinical drug screening and candidate selection, patient biobank generation for patient stratification, and even for biomarker identification. It is also important to note that the results obtained from drug screening studies in organoids have repeatedly shown a strong correlation with the subsequent clinical results seen in patients, particularly when compared to more traditional types of disease modelling.

In addition to the aforementioned use-cases, HUB organoids have also been combined with Mimetas’ OrganoPlate Graft technology, which is a microfluidics organ-on-a-chip device that is compatible with regular lab equipment and can be used in various different automated processes. OrganoPlate Graft technology provides a number of advantages over other traditional models, such as provision of a membrane-free environment, pump-free continuous perfusion, 3D cell culture option, throughput capabilities and excellent imaging capabilities. In addition, OrganoPlate Graft technology has a set of unique biological capabilities, including:

  • Barrier tissues, which can be grown in tubular structures

  • Vascularised tissues- spheroids, organoids and tissue explants can be vascularised in the OrganoPlate Graft via a gradient of angiogenic factors, which benefits internal perfusion.

  • Co-cultures i.e. introduction of diverse cell types in a single chip, which is possible due to Extracellular Matrix (ECM) patterning. This allows multiple tissue sources to be used.

  • Immunocompetent models, which have been developed so immune cells can freely move across the ECM and microfluidic channels, enabling a wide range of biological applications including in immuno-oncology.

For the combination of HUB organoids with OrganoPlate Graft technology, primary intestinal organoids were grown as tubular structures in a 3 lane OrganoPlate. When the structure was subsequently imaged, expression of the brush border markers Ezrin and Villin was observed, as well as the formation of tight junctions represented by ZO-1 staining. In addition, a major advantage of using primary material to model gut biology was the presence of various cell types, including Goblet cells (stained for Muc2 marker) and Paneth cells (stained for lysozyme). Furthermore, the tubular structure of these models allowed for access to both the apical and basal sides, which together express various drug transporters.

The OrganoPlate/HUB organoids platform opens new doors for complex tissue and disease modelling, with great potential for early drug discovery and development. As mentioned, this platform has a number of applications in the oncology field and we will continue to follow it closely as it is further developed.

Want to know more about Organoid Technology? Check out our eBook: 'Organoids as Cancer Models' to read more about the many possible uses of organoids in drug development.

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