Synthetic hydrogels for human intestinal organoid generation and colonic wound repair

• Published in: Nature cell biology Vol. 19; no. 11; pp. 1326 - 1335
• Main Authors: Cruz-Acuña, Ricardo, Quirós, Miguel, Farkas, Attila E., Dedhia, Priya H., Huang, Sha, Siuda, Dorothée, García-Hernández, Vicky, Miller, Alyssa J., Spence, Jason R., Nusrat, Asma, García, Andrés J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2017; Nature Publishing Group
• Subjects: 13; 13/100; 13/106; 13/107; 631/136/532/2064; 631/136/532/2437; 631/532/489; 631/61/338/552; 64; Animals; Cancer Research; Cell Biology; Cell Differentiation - drug effects; Cells, Cultured; Colon - drug effects; Developmental Biology; Engraftment; Equipment and supplies; Extracellular matrix; Extracellular Matrix - drug effects; Gels (Pharmacy); Humans; Hydrogels; Hydrogels - pharmacology; Intestinal Mucosa - drug effects; Intestine; Intestines - drug effects; Life Sciences; Methods; Mice; Mucosa; Organoids; Organoids - drug effects; Pluripotency; Pluripotent Stem Cells - drug effects; Polyethylene glycol; Regeneration - drug effects; Repair; Stem Cells; Transplantation; Tumors; Wound healing; Wound Healing - drug effects; United States
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb3632

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. Cruz-Acuña et al.  develop synthetic hydrogels that support the generation and expansion of viable human intestinal organoids from pluripotent stem cells and can be used as injectable vehicles for organoid engraftment and wound healing.