Nonadhesive Alginate Hydrogels Support Growth of Pluripotent Stem Cell-Derived Intestinal Organoids

Stem Cell Reports. 2019 Feb 12;12(2):381-394. doi: 10.1016/j.stemcr.2018.12.001. Epub 2019 Jan 3.


Human intestinal organoids (HIOs) represent a powerful system to study human development and are promising candidates for clinical translation as drug-screening tools or engineered tissue. Experimental control and clinical use of HIOs is limited by growth in expensive and poorly defined tumor-cell-derived extracellular matrices, prompting investigation of synthetic ECM-mimetics for HIO culture. Since HIOs possess an inner epithelium and outer mesenchyme, we hypothesized that adhesive cues provided by the matrix may be dispensable for HIO culture. Here, we demonstrate that alginate, a minimally supportive hydrogel with no inherent cell instructive properties, supports HIO growth in vitro and leads to HIO epithelial differentiation that is virtually indistinguishable from Matrigel-grown HIOs. In addition, alginate-grown HIOs mature to a similar degree as Matrigel-grown HIOs when transplanted in vivo, both resembling human fetal intestine. This work demonstrates that purely mechanical support from a simple-to-use and inexpensive hydrogel is sufficient to promote HIO survival and development.

Keywords: alginate; enteroid; human pluripotent stem cell; hydrogel; intestinal organoid; intestine; organoid.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alginates / pharmacology*
  • Animals
  • Cell Differentiation / drug effects
  • Cell Line
  • Collagen / pharmacology
  • Drug Combinations
  • Epithelium / drug effects
  • Extracellular Matrix / drug effects
  • Humans
  • Hydrogels / pharmacology*
  • Intestines / drug effects*
  • Laminin / pharmacology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Organoids / drug effects*
  • Pluripotent Stem Cells / drug effects*
  • Proteoglycans / pharmacology
  • Tissue Engineering / methods


  • Alginates
  • Drug Combinations
  • Hydrogels
  • Laminin
  • Proteoglycans
  • matrigel
  • Collagen