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Synthetic Hydrogels for Human Intestinal Organoid Generation and Colonic Wound Repair

Synthetic Hydrogels for Human Intestinal Organoid Generation and Colonic Wound Repair

Ricardo Cruz-Acuña, Miguel Quirós, Attila E Farkas, Priya H Dedhia, Sha Huang, Dorothée Siuda, Vicky García-Hernández, Alyssa J Miller, Jason R Spence, Asma Nusrat, Andrés J García

Nat Cell Biol. 2017 Nov;19(11):1326-1335.

PMID: 29058719

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
LS741177	Poly(ethylene glycol), α-maleimidopropionamide-ω-formyl terminated			Price

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