Tubuloids derived from human adult kidney and urine for personalized disease modeling

• Published in: Nature biotechnology Vol. 37; no. 3; pp. 303 - 313
• Main Authors: Schutgens, Frans, Rookmaaker, Maarten B, Margaritis, Thanasis, Rios, Anne, Ammerlaan, Carola, Jansen, Jitske, Gijzen, Linda, Vormann, Marianne, Vonk, Annelotte, Viveen, Marco, Yengej, Fjodor Yousef, Derakhshan, Sepide, de Winter-de Groot, Karin M., Artegiani, Benedetta, van Boxtel, Ruben, Cuppen, Edwin, Hendrickx, Antoni P. A., van den Heuvel-Eibrink, Marry M., Heitzer, Ellen, Lanz, Henriette, Beekman, Jeffrey, Murk, Jean-Luc, Masereeuw, Rosalinde, Holstege, Frank, Drost, Jarno, Verhaar, Marianne C, Clevers, Hans
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2019; Nature Publishing Group
• Subjects: 631/1647/767; 631/61/2320; Acute kidney failure; Adult; Adult Stem Cells - cytology; Adult Stem Cells - metabolism; Agriculture; Analysis; Animals; Biochips; Bioinformatics; Biomedical and Life Sciences; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Cell Culture Techniques - methods; Cell Differentiation - genetics; Chromosomes; Conformation; Cystic fibrosis; Cystic kidney; Diagnosis; Epithelial cells; Gene expression; Growth; Humans; Immunofluorescence; Kidney - cytology; Kidney - growth & development; Kidney Diseases; Kidneys; Life Sciences; Mice; Microfluidics; Nephrons - cytology; Nephrons - metabolism; Organoids; Organoids - cytology; Organoids - metabolism; Precision Medicine; Stem cells; Three dimensional models; Tumors; Urine; Urine - cytology; Viruses; WAGR syndrome
• ISSN: 1087-0156; 1546-1696; 1546-1696
• DOI: 10.1038/s41587-019-0048-8

Adult stem cell-derived organoids are three-dimensional epithelial structures that recapitulate fundamental aspects of their organ of origin. We describe conditions for the long-term growth of primary kidney tubular epithelial organoids, or ‘tubuloids’. The cultures are established from human and mouse kidney tissue and can be expanded for at least 20 passages (>6 months) while retaining a normal number of chromosomes. In addition, cultures can be established from human urine. Human tubuloids represent proximal as well as distal nephron segments, as evidenced by gene expression, immunofluorescence and tubular functional analyses. We apply tubuloids to model infectious, malignant and hereditary kidney diseases in a personalized fashion. BK virus infection of tubuloids recapitulates in vivo phenomena. Tubuloids are established from Wilms tumors. Kidney tubuloids derived from the urine of a subject with cystic fibrosis allow ex vivo assessment of treatment efficacy. Finally, tubuloids cultured on microfluidic organ-on-a-chip plates adopt a tubular conformation and display active (trans-)epithelial transport function. ‘Tubuloids’ grown from human kidney tissue and urine aid the study of BK virus infection, Wilms tumors and cystic fibrosis.