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Nat Biotechnol. 2019 Mar;37(3):303-313. doi: 10.1038/s41587-019-0048-8. Epub 2019 Mar 4.

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

Author information

1
Hubrecht Institute-Royal Netherlands Academy of Arts and Sciences, Utrecht, the Netherlands.
2
Department of Nephrology and Hypertension, University Medical Centre Utrecht, Utrecht, the Netherlands.
3
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands.
4
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, the Netherlands.
5
Mimetas, Organ-on-a-chip Company, Leiden, the Netherlands.
6
Regenerative Medicine Center Utrecht, Utrecht, the Netherlands.
7
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, the Netherlands.
8
Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, the Netherlands.
9
Center for Molecular Medicine, Cancer Genomics Netherlands, Department of Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
10
Institute of Human Genetics, Medical University of Graz, Graz, Austria.
11
Laboratory of Medical Microbiology and Immunology, St. Elisabeth TweeSteden Ziekenhuis, Tilburg, the Netherlands.
12
Hubrecht Institute-Royal Netherlands Academy of Arts and Sciences, Utrecht, the Netherlands. h.clevers@hubrecht.eu.
13
Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands. h.clevers@hubrecht.eu.

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.

PMID:
30833775
DOI:
10.1038/s41587-019-0048-8
[Indexed for MEDLINE]

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