| Literature DB >> 30833775 |
Frans Schutgens1,2, Maarten B Rookmaaker2, Thanasis Margaritis3, Anne Rios3, Carola Ammerlaan1,2, Jitske Jansen4, Linda Gijzen5, Marianne Vormann5, Annelotte Vonk6, Marco Viveen7, Fjodor Yousef Yengej1,2, Sepide Derakhshan3, Karin M de Winter-de Groot8, Benedetta Artegiani1, Ruben van Boxtel3, Edwin Cuppen9, Antoni P A Hendrickx7, Marry M van den Heuvel-Eibrink3, Ellen Heitzer10, Henriette Lanz5, Jeffrey Beekman6, Jean-Luc Murk4,11, Rosalinde Masereeuw4, Frank Holstege3, Jarno Drost3, Marianne C Verhaar2, Hans Clevers12,13.
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.Entities:
Mesh：
Year: 2019 PMID： 30833775 DOI： 10.1038/s41587-019-0048-8
Source DB: PubMed Journal: Nat Biotechnol ISSN： 1087-0156 Impact factor: 68.164