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

Frans Schutgens, Maarten B. Rookmaaker, Thanasis Margaritis, Anne Rios, Carola Ammerlaan, Jitske Jansen, Linda Gijzen, Marianne Vormann, Annelotte Vonk, Marco Viveen, Fjodor Yousef Yengej, Sepide Derakhshan, Karin M. de Winter-de Groot, Benedetta Artegiani, Ruben van Boxtel, Edwin Cuppen, Antoni P. A. Hendrickx, Marry M. van den Heuvel-Eibrink, Ellen Heitzer, Henriette LanzJeffrey Beekman, Jean-Luc Murk, Rosalinde Masereeuw, Frank Holstege, Jarno Drost, Marianne C. Verhaar, Hans Clevers

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)303-313
JournalNature Biotechnology
Volume37
Issue number3
DOIs
Publication statusPublished - 1 Mar 2019
Externally publishedYes

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