Scientists Engineer Intestinal Tissue With Nerve Supply

Intestinal tissue containing functional nerves engineered in the laboratory can be used as a good model to study Hirschsprung disease. The researchers who developed and conducted studies on the tissue published their work in the Nature Medicine. Our intestines carry out the important function of digesting and absorbing nutrients from the food we eat, and further propelling unwanted material out of the body. Like for other involuntary muscles, the function of the intestines is controlled by nerves of the autonomic nervous system. This explains why stressful conditions alter the movements of the intestines, often resulting in a condition called irritable bowel syndrome.

Researchers have earlier developed intestinal tissue in the laboratory to study various intestinal functions using cells called pluripotent stem cells. These cells have the ability to transform into any types of cells, and under the right conditions, form intestinal cells. However, the intestinal tissue did not have nerve cells, and therefore could not replicate the exact functioning of the human intestine.

Moving a step forward, researchers introduced neural crest cells into the growing intestinal cells at the right time, and were able to develop intestinal tissue with nerve supply. The tissue resembled human intestinal tissue in terms of structure as well as function.

The researchers used the tissue to study a condition called Hirschsprung Disease or toxic megacolon. Hirschsprung disease is a genetic disorder where the wall of the large intestine lacks nerves and therefore cannot contract. The researchers introduced a mutation in the gene PHOX2B, which occurs in Hirschsprung disease. They were able to demonstrate that the mutation affects the nerves of the intestine, similar to Hirschsprung disease.

The newly developed tissue has several potential uses in research as well as therapeutics. It can be used to study other intestinal conditions like necrotizing enterocolitis. It can also be used as a medium to test medications before they can enter clinical trials. This form of testing can prove if the drug can produce symptoms like diarrhea and cramps.

From a therapeutic point of view, the tissue has the potential to be used for transplantation. Such use of the tissue will reduce the dependency on donors and reduce waiting time for transplantation. In fact, the researchers were able to transplant the tissue into laboratory mice and found that it functions just like the normal intestine.

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Reference

1. Workman MJ et al. Engineered human pluripotent-stem-cell-derived intestinal tissues with a functional enteric nervous system. Nature Medicine, 2016; DOI: 10.1038/nm.4233

Source-Medindia