Key Points
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The development of in vitro and in vivo modelling systems that accurately reflect the diverse mutational profiles of urological diseases is crucial
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Patient-derived organoids in 3D culture systems enable the culturing of stem or progenitor cells for urological organs and they also mimic the in vivo microenvironment and stromal interactions of cancer cells
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Nephron progenitor cells derived from human pluripotent stem cells have been successfully used to form complex multicellular kidney organoids, which have potential in disease modelling and drug screening
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Organoids can be used to model disease; use of gene editing tools enables the study of the mechanisms of tumorigenesis and restoration of the functional defects caused by genetic lesions
Abstract
Technical advances in the development of organoid systems enable cell lines, primary adult cells, or stem or progenitor cells to develop into diverse, multicellular entities, which can self-renew, self-organize, and differentiate. These 3D organoid cultures have proven to be of value in increasing our understanding of the biology of disease and offer the potential of regenerative and genetic therapies. The successful application of 3D organoids derived from adult tissue into urological cancer research can further our understanding of these diseases and could also provide preclinical cancer models to realize the precision medicine paradigm by therapeutic screening of individual patient samples ex vivo. Kidney organoids derived from induced pluripotent stem cells provide personalized biomarkers, which can be correlated with genetic and clinical information. Organoid models can also improve our comprehension of aspects of particular diseases; for example, in prostate cancer, 3D organoids can aid in the identification of tumour-initiating cells from an epithelial cell lineage. Furthermore, kidney organoid differentiation from human pluripotent stem cells enables gene editing to model disease in kidney tubular epithelial cells. State-of-the-art human organoid cultures have potential as tools in basic and clinical research in renal, bladder, and prostatic diseases.
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Acknowledgements
We thank Margaret McPartland for providing editorial input. Funding was providing by the National Institutes of Health (5K08CA140946 and NIH Cancer Center Core Grant P30 CA008748, and SPORE in Prostate Cancer (5P50CA092629-15)), US Department of Defense (W81XWH-10-1-0197), the Geoffrey Beene Cancer Center, the STARR Cancer Consortium (I8-A722), a Stand Up To Cancer–Prostate Cancer Foundation Prostate Dream Team Translational Research Grant (SU2CAACR-DT0712), and a Prostate Cancer Foundation Movember Challenge Grant.
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Wang, S., Gao, D. & Chen, Y. The potential of organoids in urological cancer research. Nat Rev Urol 14, 401–414 (2017). https://doi.org/10.1038/nrurol.2017.65
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