Disease modeling and cancer therapy in stem cell-derived 3D organoid systems
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United States of America
25 October 2018
Thermo Fisher Scientific/Gibco
While the significance of the microbiome is unprecedented, a thorough study to dissect the role of individual populations of the natural gut microbiome in healthy and diseased states is still lacking. Currently available in-vitro models of the human intestine have certain limitations, e.g., lack of immune cells or microbiota. Therefore, systems closely mirroring the human intestine are needed to gain a better understanding of intestinal dysfunction, host - pathogen interactions and for the development of more effective therapies for cancer. It is important to establish a patient derived, fast and efficient system which would mimic the in-vivo architecture in humans and permit precise studies on interactions of the gut microbes with the epithelium and the immune cells. The in-vitro 3D “mini-gut” system developed in the Clevers lab displays many important functions of the normal intestinal epithelium. Along with the developed toolbox for the analysis of these organoids (including FACS-based cell sorting, confocal imaging, RNA Sequencing, mass-spec proteomics and CRISPR-Cas9), it has proven to serve as a powerful system to investigate regulatory and pathological mechanisms of the intestinal epithelium on a molecular level.
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In vitro methods
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To this end, we are developing a triple co-culture system of epithelial cells, immune cells and microbes to better understand the functional role of the gut microbiota, enabling personalized healthcare for the benefit of patients suffering from GI tract diseases. It might be possible in the future to determine the microbiome composition of cancer patients and provide personalized immunotherapy drug treatment.
Organoids can be used for studying cancer and hereditary diseases, as well as in the examination of host cell–microorganism interactions.
Patient-derived organoids may enable personalized medicine.
Identify categories of individuals at risk of acquiring HDV infection.
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