Tubuloids Derived from Human Adult Kidney and Urine for Personalized Disease Modeling

Overview

Journal Nat Biotechnol

Specialty Biotechnology

Date 2019 Mar 6

PMID 30833775

Citations 174

Authors

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 Lanz

Jeffrey Beekman

Jean-Luc Murk

Rosalinde Masereeuw

Frank Holstege

Jarno Drost

Marianne C Verhaar

Hans Clevers

Affiliations

Soon will be listed here.

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.

Citing Articles

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