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Biological Chemistry

Intestinal grafts grown from stem cells

Engineered tissue absorbs and transfers nutrients, could be used to enhance or restore intestinal function

by Celia Henry Arnaud
October 16, 2017 | A version of this story appeared in Volume 95, Issue 41

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Credit: Kentaro Kitano
A small-intestine scaffold with the original cells removed has been repopulated with human-stem-cell-derived endothelial cells (green) and with blood vessel cells (red). The overall length of the segment is 4 cm.
Fluorescence micrograph of a small intestinal scaffold that has been recellularized by stem-cell-derived epithelial cells.
Credit: Kentaro Kitano
A small-intestine scaffold with the original cells removed has been repopulated with human-stem-cell-derived endothelial cells (green) and with blood vessel cells (red). The overall length of the segment is 4 cm.

Gastrointestinal disorders such as Crohn’s disease can lead to a condition known as short bowel syndrome (SBS) in which a significant portion of a person’s small intestine is no longer capable of absorbing nutrients. Intestinal grafts to supplement the remaining small intestine could help restore this lost function. A team led by Harald C. Ott of Massachusetts General Hospital has grown functional intestinal tissue by seeding scaffolds formed from rat small intestines with human pluripotent stem cells (Nat. Commun. 2017, DOI: 10.1038/s41467-017-00779-y). The researchers remove all cells from a segment of rat small intestine to form a scaffold that retains the extracellular architecture of the original tissue. They direct the human stem cells to differentiate into intestinal progenitor cells and then use them to seed the scaffold. After two weeks in culture, the progenitor cells produce many of the cell types usually found in intestinal tissue. The researchers also add human umbilical cells to regrow blood vessels. The regenerated tissue is able to take up and transport glucose and fatty acids through the vasculature, with grafts transplanted into immunodeficient rats surviving and functioning for at least four weeks. Adding “bioengineered constructs as small segments of additional absorptive surface area could become a treatment option for nutrient intake in SBS in the future,” the researchers write.

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