Intestine grown from stem cells could improve on mouse models of gut disorders

Stem cell
Tufts scientists used stem cells and silk to build a realistic model of the human small intestine.

Scientists at Tufts University have created a 3D model of the human small intestine—an “organ on a chip” that they believe could be used to study inflammatory bowel disease (IBD) and infectious disorders of the gut. The model mimics many of the functions of the real thing, including innate immune responses.

The team used a scaffold made of silk to cultivate “enteroids,” which are cells found in the epithelium of the intestinal walls. The enteroids were derived from human stem cells. They discovered that the cells in the structure differentiated into a complete epithelium layer with four distinct intestinal cell types, they reported in the journal PLOS One.

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The 3D intestinal model had many of the same characteristics of a human intestine, including the ability to secrete digestive enzymes and the tight junctions typically found in the organ. They believe those characteristics would give the scaffold the ability to replicate a realistic human response to infections of the gut. The model might also be used to study how IBD develops, they said in their paper.

The Tufts team tested that hypothesis by infecting their system with E. coli. The scaffold launched an antibacterial response, they said, and turned on genes known to be involved in immune responses.

This research follows a similar endeavor at Tufts’ Boston neighbor, Harvard, where scientists at the Wyss Institute for Biologically Inspired Engineering made a model of intestinal inflammation out of a flexible polymer that was designed to mimic the fluidic movements of the human gut. In 2015, they reported they could use their system to culture living cells from both diseased and healthy human guts, so they could unravel the pathology of IBD.

More recently, some efforts to commercialize organ-on-a-chip technologies have drummed up investor interest. Last fall, one major player in that space, Emulate, raised a $17 million Series B funding and landed a development deal with Covance. Emulate is working on models of the kidney, intestine, liver, skin and other organs.

The goal of many who are working in the organ-on-a-chip space is to replace rodent models of disease with technology. That’s because preclinical research performed in animals often doesn’t translate well to people. In fact, the Tufts researchers believe their silk model of the small intestine could replace mice and rats, providing a more realistic model that can bridge the gap between cell-culture research and human clinical trials.