Engineered Kidney Tubules for Modeling Patient-Specific Diseases and Drug Discovery

Valentina Benedetti, Valerio Brizi, Patrizia Guida, Susanna Tomasoni, Osele Ciampi, Elena Angeli, Ugo Valbusa, Ariela Benigni, Giuseppe Remuzzi, Christodoulos Xinaris

Research output: Contribution to journalArticle

Abstract

The lack of engineering systems able to faithfully reproduce complex kidney structures in vitro has made it difficult to efficiently model kidney diseases and development. Using polydimethylsiloxane (PDMS) scaffolds and a kidney-derived cell line we developed a system to rapidly engineer custom-made 3D tubules with typical renal epithelial properties. This system was successfully employed to engineer patient-specific tubules, to model polycystic kidney disease (PKD) and test drug efficacy, and to identify a potential new pharmacological treatment. By optimizing our system we constructed functional ureteric bud (UB)-like tubules from human induced pluripotent stem cells (iPSCs), and identified a combination of growth factors that induces budding morphogenesis like embryonic kidneys do. Finally, we applied this assay to investigate budding defects in UB-like tubules derived from a patient with a PAX2 mutation. Our system enables the modeling of human kidney disease and development, drug testing and discovery, and lays the groundwork for engineering anatomically correct kidney tissues in vitro and developing personalized medicine applications.

Original languageEnglish
Pages (from-to)253-268
Number of pages16
JournalEBioMedicine
Volume33
DOIs
Publication statusPublished - Jul 2018

Keywords

  • Animals
  • Cell Differentiation
  • Dogs
  • Drug Discovery
  • Drug Evaluation, Preclinical
  • Humans
  • Induced Pluripotent Stem Cells/cytology
  • Kidney Tubules/cytology
  • Madin Darby Canine Kidney Cells
  • Models, Biological
  • Mutation
  • Organ Culture Techniques/methods
  • PAX2 Transcription Factor/genetics
  • Polycystic Kidney Diseases/genetics
  • Precision Medicine
  • Tissue Scaffolds

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