Non-animal model systems such as organoids and Organ-on-Chip (OoC) can be developed from a variety of organ systems and used as a complementary approach and/or alternative for a subset of in vivo experiments. Within the MCCA, the Hubrecht Institute (Utrecht), Erasmus MC (Rotterdam) and the Princess Máxima Center (Utrecht), who are leading in this field, are joining forces in the endeavors to combat cancer and aging.
The Netherlands plays an important role in developing alternatives for animal experiments, both organoid technology and culturing of tumor tissue slices, accompanied by the development of multi-omics imaging and transcriptomics platforms. Together, these technologies fill the gap between cell line experiments and laboratory animal approaches.
The aim of the non-animal facility is to share expertise and capacity to generate, maintain, and manipulate non-animal model systems from different origins. In addition, they provide the associated high-tech infrastructure and knowledge for multi-omics 3D imaging and transcriptomics tool to offer in depth readouts tailored to the complexity modeled in these systems. As such, the efficient translation of basic research into novel treatments for patients can be achieved.
Human organoids can be grown from tissue from healthy donors and patients. They maintain the original architecture and physiology. This model system can be exploited as a platform for many purposes: tumor growth, genetic and infectious diseases, and biobanking of samples; for drug screening, toxicology assays and gene therapy. In the future, we want to generate complex (immune)-organoid co-cultures and optimize our protocols for genetic manipulations of organoids.
We are also exploring the establishment of cultured conditions for tumor slices. It allows proliferation at physiological rates and maintains tissue morphology and viability. We recently adapted this to the Organ-on-Chip (OoC) concept, and placed the tissue slice in a microfluidic setting. It mimics organ function and disease states more closely and shows predictive therapeutic value of the tissue reactions. We will expand the different applications and will closely collaborate with TU Delft to generate new developments.
Advanced 3D microscope technologies are developed to image intact specimens and can be accompanied by Artificial Intelligence (AI) driven analytical pipelines. In multi-omics platforms, single-cell imaging and sequencing data are integrated. This can, for instance, be used to decipher the phenotypic landscape of immune cells that target cancer. All this will be readily shared with the scientific community. We will optimize and share imaging protocols and AI-based automated analysis pipelines tailored to novel disease models.
All three institutes offer their expertise and infrastructure to generate, maintain and manipulate organoids and OoC from diverse origin (murine and human) for a variety of experiments; as a service or in close collaboration with other parties. In addition, they can provide advice, support and training in high-dimensional fixed and live cell 3D imaging technologies, including the development of required 3D imaging data analysis and multi-omics data integration pipelines.
Anne Rios - Princess Máxima Center, Utrecht, The Netherlands
Hans Clevers - Hubrecht Institute, Utrecht, The Netherlands
Ronald Kanaar - Erasmus MC, Rotterdam, The Netherlands