Tubuloid culture enables long-term expansion of functional human kidney tubule epithelium from iPSC-derived organoids

Fjodor A Yousef Yengej, Jitske Jansen, Carola M E Ammerlaan, Emre Dilmen, Carla Pou Casellas, Rosalinde Masereeuw, Joost G Hoenderop, Bart Smeets, Maarten B Rookmaaker, Marianne C Verhaar, Hans Clevers

Research output: Contribution to journal/periodicalArticleScientificpeer-review

7 Citations (Scopus)

Abstract

Kidney organoids generated from induced pluripotent stem cells (iPSC) have proven valuable for studies of kidney development, disease, and therapeutic screening. However, specific applications have been hampered by limited expansion capacity, immaturity, off-target cells, and inability to access the apical side. Here, we apply recently developed tubuloid protocols to purify and propagate kidney epithelium from d7+18 (post nephrogenesis) iPSC-derived organoids. The resulting 'iPSC organoid-derived (iPSCod)' tubuloids can be exponentially expanded for at least 2.5 mo, while retaining expression of important tubular transporters and segment-specific markers. This approach allows for selective propagation of the mature tubular epithelium, as immature cells, stroma, and undesirable off-target cells rapidly disappeared. iPSCod tubuloids provide easy apical access, which enabled functional evaluation and demonstration of essential secretion and electrolyte reabsorption processes. In conclusion, iPSCod tubuloids provide a different, complementary human kidney model that unlocks opportunities for functional characterization, disease modeling, and regenerative nephrology.

Original languageEnglish
Pages (from-to)e2216836120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number6
DOIs
Publication statusPublished - 07 Feb 2023

Keywords

  • Humans
  • Induced Pluripotent Stem Cells/metabolism
  • Kidney/metabolism
  • Epithelium
  • Organoids/metabolism
  • Kidney Tubules
  • Cell Differentiation

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