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Kidney Week

Abstract: PO0628

Human Induced Pluripotent Stem Cell-Derived Kidney Organoids to Model Idiopathic and Congenital Nephrotic Syndrome

Session Information

Category: Development, Stem Cells, and Regenerative Medicine

  • 500 Development, Stem Cells, and Regenerative Medicine


  • Jansen, Jitske, Radboudumc, Nijmegen, Gelderland, Netherlands
  • van den Berge, Bartholomeus Tideman, Radboudumc, Nijmegen, Gelderland, Netherlands
  • van den Broek, Martijn, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Willemsen, Brigith, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Kuppe, Christoph, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, Nordrhein-Westfalen, Germany
  • Di Giovanni, Gianluca Vincenzo, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Mooren, Fieke, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Parr, Naomi, Radboudumc, Nijmegen, Gelderland, Netherlands
  • den Braanker, Dirk, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Maas, Rutger J., Radboudumc, Nijmegen, Gelderland, Netherlands
  • Wetzels, Jack F., Radboudumc, Nijmegen, Gelderland, Netherlands
  • Van De Kar, Nicole, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Kramann, Rafael, Rheinisch-Westfalische Technische Hochschule Aachen, Aachen, Nordrhein-Westfalen, Germany
  • Van der vlag, Johan, Radboudumc, Nijmegen, Gelderland, Netherlands
  • Schreuder, Michiel F., Radboudumc, Nijmegen, Gelderland, Netherlands
  • Smeets, Bart, Radboudumc, Nijmegen, Gelderland, Netherlands

Recent advances in human stem cell-derived kidney organoid models have opened new avenues to accurately model podocytopathies in 3D in vitro. The aim of this study is to develop and characterize human induced pluripotent stem cells (iPSC)-derived 3D kidney organoids as a first step in modeling idiopathic and congenital nephrotic syndrome (NS) in vitro.


Human iPSC were successfully cultured into kidney organoids and characterized using scRNA sequencing, immunocytochemistry, TEM and RNAscope. The protamine sulphate (PS) model and FSGS plasma treatment were used to model idiopathic NS. Podocin mutant organoids were used to study congenital NS.


Kidney organoids showed a clear podocyte population expressing, amongst others, podocin, nephrin, PLA2R, WT1, VEGFA and collagen IV alpha 3. The slit diaphragm was confirmed by TEM. To model podocyte injury, organoids were exposed to protamine sulphate (PS) or active FSGS plasma. PS-induced injury in organoids showed clear podocyte cytoskeleton rearrangements and the induction of pNPHS1-1176 protein expression. The induced podocyte injury was rescued by heparin sulphate, illustrating recovery of injury associated mechanisms in 3D podocytes. The PS effect was organoid-podocyte specific as their 2D iPS-derived podocyte counterparts did not express pNPHS1-1176. Organoids exposed to active FSGS plasma for 4h showed increased granule formation, a podocyte stress marker, in NPHS1+ podocytes which was less abundant when treated with remission plasma.
To model congenital nephropathy, erythroblasts from a pediatric patient with compound heterozygous mutations p.Arg138Gln (exon 3) and p.Asp160Tyr (exon 4) in the podocin (NPHS2) gene, were successfully reprogrammed in iPSC. Aberrant localization and weak podocin expression was shown in organoids. Using CRISPR/Cas9 the exon 3 mutation was repaired and podocin expression was restored.


We successfully developed human iPSC-derived kidney organoids that will serve as a state-of-the-art tool to accurately study podocytopathies in a dish.


  • Other NIH Support