Synthetic hydrogels for human intestinal organoid generation and colonic wound repair

  • Nat Cell Biol. 2017 Nov;19(11):1326-1335. doi: 10.1038/ncb3632.
Ricardo Cruz-Acuña  1  2 ,  Miguel Quirós  3 ,  Attila E Farkas  4 ,  Priya H Dedhia  5  6  7 ,  Sha Huang  5  6  7 ,  Dorothée Siuda  3 ,  Vicky García-Hernández  3 ,  Alyssa J Miller  5 ,  Jason R Spence  5  6  7 ,  Asma Nusrat  3 ,  Andrés J García  2  8
Affiliations
  • 1. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
  • 2. Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
  • 3. Department of Pathology, University of Michigan, Ann Arbor, Michigan 48104, USA.
  • 4. Institute of Biophysics, Biological Research Centre, Hungarian Academy of Sciences, Szeged 6726, Hungary.
  • 5. Department of Internal Medicine, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan 48104, USA.
  • 6. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan 48104, USA.
  • 7. Center for Organogenesis, University of Michigan Medical School, Ann Arbor, Michigan 48104, USA.
  • 8. George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
PMID: 29058719 DOI: 10.1038/ncb3632
Abstract

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.