TY - JOUR
T1 - Tubuloids derived from human adult kidney and urine for personalized disease modeling
AU - Schutgens, Frans
AU - Rookmaaker, Maarten B
AU - Margaritis, Thanasis
AU - Rios, Anne
AU - Ammerlaan, Carola
AU - Jansen, Jitske
AU - Gijzen, Linda
AU - Vormann, Marianne
AU - Vonk, Annelotte
AU - Viveen, Marco
AU - Yengej, Fjodor Yousef
AU - Derakhshan, Sepide
AU - de Winter-de Groot, Karin M
AU - Artegiani, Benedetta
AU - van Boxtel, Ruben
AU - Cuppen, Edwin
AU - Hendrickx, Antoni P A
AU - van den Heuvel-Eibrink, Marry M
AU - Heitzer, Ellen
AU - Lanz, Henriette
AU - Beekman, Jeffrey
AU - Murk, Jean-Luc
AU - Masereeuw, Rosalinde
AU - Holstege, Frank
AU - Drost, Jarno
AU - Verhaar, Marianne C
AU - Clevers, Hans
N1 - Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
KW - Adult
KW - Adult Stem Cells/cytology
KW - Animals
KW - Cell Culture Techniques/methods
KW - Cell Differentiation/genetics
KW - Humans
KW - Kidney/cytology
KW - Kidney Diseases
KW - Mice
KW - Nephrons/cytology
KW - Organoids/cytology
KW - Precision Medicine
KW - Urine/cytology
UR - http://www.scopus.com/inward/record.url?scp=85062392466&partnerID=8YFLogxK
U2 - 10.1038/s41587-019-0048-8
DO - 10.1038/s41587-019-0048-8
M3 - Article
C2 - 30833775
SN - 1087-0156
VL - 37
SP - 303
EP - 313
JO - Nature biotechnology
JF - Nature biotechnology
IS - 3
ER -