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

Meghan M. Capeling, Michael Czerwinski, Sha Huang, Yu Hwai Tsai, Angeline Wu, Melinda S. Nagy, Benjamin Juliar, Nambirajan Sundaram, Yang Song, Woojin M. Han, Shuichi Takayama, Eben Alsberg, Andres J. Garcia, Michael Helmrath, Andrew J. Putnam, Jason R. Spence

Research output: Contribution to journalArticlepeer-review

105 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)381-394
Number of pages14
JournalStem Cell Reports
Volume12
Issue number2
DOIs
StatePublished - 12 Feb 2019
Externally publishedYes

Keywords

  • alginate
  • enteroid
  • human pluripotent stem cell
  • hydrogel
  • intestinal organoid
  • intestine
  • organoid

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