Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 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

Frans Schutgens  1   2 , Maarten B Rookmaaker  2 , Thanasis Margaritis  3 , Anne Rios  3 , Carola Ammerlaan  1   2 , Jitske Jansen  4 , Linda Gijzen  5 , Marianne Vormann  5 , Annelotte Vonk  6 , Marco Viveen  7 , Fjodor Yousef Yengej  1   2 , Sepide Derakhshan  3 , Karin M de Winter-de Groot  8 , Benedetta Artegiani  1 , Ruben van Boxtel  3 , Edwin Cuppen  9 , Antoni P A Hendrickx  7 , Marry M van den Heuvel-Eibrink  3 , Ellen Heitzer  10 , Henriette Lanz  5 , Jeffrey Beekman  6 , Jean-Luc Murk  4   11 , Rosalinde Masereeuw  4 , Frank Holstege  3 , Jarno Drost  3 , Marianne C Verhaar  2 , Hans Clevers  12   13
Affiliations

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

Frans Schutgens et al. Nat Biotechnol. 2019 Mar.

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.

PubMed Disclaimer

Comment in

References

    1. Clevers, H. Modeling development and disease with organoids. Cell 165, 1586–1597 (2016). - DOI - PubMed
    1. Drost, J. & Clevers, H. Organoids in cancer research. Nat. Rev. Cancer 18, 407–418 (2018). - DOI - PubMed
    1. Takasato, M. et al. Kidney organoids from human iPS cells contain multiple lineages and model human nephrogenesis. Nature 526, 564–568 (2015). - DOI - PubMed
    1. Sato, T. et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262–265 (2009). - DOI - PubMed
    1. Dekkers, J. F. et al. A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat. Med. 19, 939–945 (2013). - DOI - PubMed

Publication types