Nusrat Lab and Collaborators Publish on Human Intestinal Organoid Generation in Nature Cell Biology

By Robin Kunkel | October 24 2017

ON THE COVER: Beta catenin is highlighted in green and red indicates Ki67 markers.Human intestinal organoids that were implanted in the kidney capsule of a immunocompromised mouse and grown for 8 weeks. The tissue clearly resembles adult human intestinal tissue. Beta catenin is green and chromogranin A (endocrine cell marker) is red. Photo provided by Miguel QuirosMiguel Quiros, Dorothee Siuda, Vicky Garcia-Hernandez in the laboratory of Asma Nusrat in our Department of Pathology, along with collaborators in the Michigan Medicine Departments of Internal Medicine, Cell and Developmental Biology and Center for Organogenesis, and colleagues from the Georgia Institute of Technology have published work describing “Synthetic hydrogels for human intestinal organoid generation and colonic wound repair” in Nature Cell Biology.

These investigators report that the 3D growth and differentiation of human intestinal organoids (HIO) from pluripotent stem cells could be achieved by growing them on a synthetic hydrogel macromere (ethylene glycol), containing 96% water and a cell adhesion peptide. In vitro growth of these organoids was robust and highly reproducible. In addition, these studies demonstrated that the hydrogel could act as an injection vehicle, as they were able to deliver developing organoids into the injured intestinal mucosa of mice, resulting in HIO engraftment and improved colonic wound repair.

The implanted cells were fluorescently labeled so that they could be tracked and within one month the hydrogel matrix had disappeared, the HIOs had engrafted and were forming 3D structures resembling normal tissue. In addition, they were producing their own natural extracellular matrix. "The fully defined nature of these synthetic bioengineered hydrogels could make them ideal for use in human patients in the event that HIOs are used for therapy in the future," said Miguel Quirós, a University of Michigan postdoctoral fellow and co-lead author in the study. Added Nusrat: "In this work, we demonstrated that the hydrogels facilitate the transplantation of HIOs into an injured intestine, suggesting that this technique has significant implications for treating intestinal injuries caused by diseases such as inflammatory bowel disease."

Read more about this study here.