Synthetic hydrogels for human intestinal organoid generation and colonic wound repair

Nat Cell Biol. 2017 Nov;19(11):1326-1335. doi: 10.1038/ncb3632. Epub 2017 Oct 23.


In vitro differentiation of human intestinal organoids (HIOs) from pluripotent stem cells is an unparalleled system for creating complex, multicellular three-dimensional structures capable of giving rise to tissue analogous to native human tissue. Current methods for generating HIOs rely on growth in an undefined tumour-derived extracellular matrix (ECM), which severely limits the use of organoid technologies for regenerative and translational medicine. Here, we developed a fully defined, synthetic hydrogel based on a four-armed, maleimide-terminated poly(ethylene glycol) macromer that supports robust and highly reproducible in vitro growth and expansion of HIOs, such that three-dimensional structures are never embedded in tumour-derived ECM. We also demonstrate that the hydrogel serves as an injection vehicle that can be delivered into injured intestinal mucosa resulting in HIO engraftment and improved colonic wound repair. Together, these studies show proof-of-concept that HIOs may be used therapeutically to treat intestinal injury.

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cells, Cultured
  • Colon / drug effects*
  • Extracellular Matrix / drug effects
  • Humans
  • Hydrogels / pharmacology*
  • Intestinal Mucosa / drug effects
  • Intestines / drug effects*
  • Mice
  • Organoids / drug effects*
  • Pluripotent Stem Cells / drug effects
  • Regeneration / drug effects*
  • Wound Healing / drug effects*


  • Hydrogels