Soft, Dynamic Hydrogel Confinement Improves Kidney Organoid Lumen Morphology and Reduces Epithelial-Mesenchymal Transition in Culture

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Pluripotent stem cell-derived kidney organoids offer a promising solution to renal failure, yet current organoid protocols often lead to off-target cells and phenotypic alterations, preventing maturity. Here, various dynamic hydrogel architectures are created, conferring a controlled and biomimetic environment for organoid encapsulation. How hydrogel stiffness and stress relaxation affect renal phenotype and undesired fibrotic markers are investigated. The authors observe that stiff hydrogel encapsulation leads to an absence of certain renal cell types and signs of an epithelial-mesenchymal transition (EMT), whereas encapsulation in soft, stress-relaxing hydrogels leads to all major renal segments, fewer fibrosis or EMT associated proteins, apical proximal tubule polarization, and primary cilia formation, representing a significant improvement over current approaches to culture kidney organoids. The findings show that engineering hydrogel mechanics and dynamics have a decided benefit for organoid culture. These structure-property-function relationships can enable the rational design of materials, bringing us closer to functional engraftments and disease-modeling applications.

Original languageEnglish
Article number2200543
Number of pages12
JournalAdvanced Science
Volume9
Issue number20
Early online date14 May 2022
DOIs
Publication statusPublished - Jul 2022

Keywords

  • CELLS
  • GENERATION
  • INJURY
  • MORPHOGENESIS
  • PRIMARY CILIA
  • REGENERATIVE MEDICINE
  • dynamic hydrogels
  • epithelial-mesenchymal transition
  • kidney organoids
  • primary cilia
  • viscoelastic

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