| Autor: |
Yousef Yengej FA; Hubrecht Institute for Developmental Biology and Stem Cell Research - Royal Netherlands Academy of Arts and Sciences (KNAW) & University Medical Center Utrecht, 3584 CT and 3584 CX Utrecht, Netherlands.; Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Jansen J; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, GA 6525 Nijmegen, The Netherlands.; Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Amalia Children's Hospital, GA 6525 Nijmegen, The Netherlands.; Institute of Experimental Medicine and Systems Biology, Rheinisch-Westfälische Technische Hogeschool (RWTH) Aachen University, 52074 Aachen, Germany., Ammerlaan CME; Hubrecht Institute for Developmental Biology and Stem Cell Research - Royal Netherlands Academy of Arts and Sciences (KNAW) & University Medical Center Utrecht, 3584 CT and 3584 CX Utrecht, Netherlands.; Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Dilmen E; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, GA 6525 Nijmegen, The Netherlands., Pou Casellas C; Hubrecht Institute for Developmental Biology and Stem Cell Research - Royal Netherlands Academy of Arts and Sciences (KNAW) & University Medical Center Utrecht, 3584 CT and 3584 CX Utrecht, Netherlands.; Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Masereeuw R; Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, CG 3584 Utrecht, The Netherlands., Hoenderop JG; Department of Physiology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, GA 6525 Nijmegen, The Netherlands., Smeets B; Department of Pathology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, GA 6525 Nijmegen, The Netherlands., Rookmaaker MB; Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Verhaar MC; Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands., Clevers H; Hubrecht Institute for Developmental Biology and Stem Cell Research - Royal Netherlands Academy of Arts and Sciences (KNAW) & University Medical Center Utrecht, 3584 CT and 3584 CX Utrecht, Netherlands. |
| Abstrakt: |
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. |
