Scientists use human cells to grow a fully-functional small intestine inside mouse


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Scientists have grown 'fully-functioning' human gut tissue inside a mouse - a breakthrough that could one day help many thousands suffering with intestinal disorders.

By transplanting cells from a human into a mouse, paediatric surgeons successfully grew small intestine tissue that worked just like the 'real' thing. 

Doctors hope their findings will eventually help treat a range of digestive conditions as well as boost survival rates in sufferers of diseases such as short bowel syndrome (SBS)  - a condition that kills nearly a third of young patients within five years.

Paediatrics have created tissue-engineered small intestine (Tesi) tissue (part of the small intestine's duodenum (pictured) that replicates key aspects of a functioning human intestine. During tests the tissue proved it could break down sugars into glucose and release gastrointestinal hormones

Paediatrics have created tissue-engineered small intestine (Tesi) tissue (part of the small intestine's duodenum (pictured) that replicates key aspects of a functioning human intestine. During tests the tissue proved it could break down sugars into glucose and release gastrointestinal hormones

The research was led by Dr Tracy Grikscheit from the Children's Hospital Los Angeles (CHLA).

CHLA had previously shown that tissue-engineered small intestine tissue could be 'grown' by implanting human donor tissue into mice.

However, in initial studies - published in 2011 in the biomedical journal Tissue Engineering, Part A - the intestine created had a limited range of functions.

As part of the new study, the researchers created Tesi that replicates key aspects of a functioning human intestine.

In particular, the Tesi developed contains the mucosal lining - or barrier - seen in fully-grown intestines.

THE ROLE OF THE SMALL INTESTINE

The small intestine is a tubular structure that carries food from the stomach up to the colon and its main function is to help with digestion.

The small intestine increases 20 times in length as a person ages, from around 78 inches (200cm) in a newborn baby, to almost six metres (20 feet) long.

It is typically three times the height of the child or adult and is the part of the intestines where 90 per cent of digestion and food absorption takes place.

The remaining 10 per cent occurs in the stomach and large intestine.

As food travels through the small intestine, it absorbs nutrients and minerals.

Chemical digestion uses enzymes to break down food into a form that can then be absorbed into tissues of the body.

Once at the colon, the large intestine carries it to the rectum. The main function of this organ is to aid in digestion.

And, during tests the Tesi proved it could break down sugars into glucose and release gastrointestinal hormones.

Mice were chosen for the study because mouse Tesi is 'highly similar' to the Tesi derived from human cells.

For example, both contain important building blocks such as the stem and progenitor cells that continue to regenerate the intestine as a living tissue replacement.

The researchers took cells from human intestine tissue and soaked them in a digestive enzyme solution.

This solution was fitted onto a so-called polymer scaffold - a structure used to help the cells and tissue develop - which was then implanted into a mouse.

Four weeks later, the Tesi was harvested and tested.

Scientists discovered it was able to break down sugars into glucose, and found the cells within the engineered tissue developed in close proximity to other specialised cells.

These specialised cells are said to be necessary in healthy human intestine to create a fully functioning organ.

'We have shown that we can grow tissue-engineered small intestine that is more complex than other stem cell or progenitor cell models that are currently used to study intestinal regeneration and disease, and proven it to be fully functional as it develops from human cells,' said Dr Grikscheit.

'Demonstrating the functional capacity of this tissue-engineered intestine is a necessary milestone on our path toward one day helping patients with intestinal failure.'

Mice (stock image) were chosen for the study because mouse Tesi is 'highly similar' to Tesi from human cells. The researchers took cells from human intestines and soaked them in a digestive enzyme solution, which was then implanted into a mouse. Four weeks later, the Tesi was harvested and succesfully tested

Mice (stock image) were chosen for the study because mouse Tesi is 'highly similar' to Tesi from human cells. The researchers took cells from human intestines and soaked them in a digestive enzyme solution, which was then implanted into a mouse. Four weeks later, the Tesi was harvested and succesfully tested

The research was published in the American Journal of Physiology: GI & Liver, and brings surgeons a step closer to helping human patients using this regenerative medicine technique.

In particular, it could be used to treat short bowel syndrome - a major cause of intestinal failure, particularly in premature babies and newborns with congenital intestinal problems.

Tesi may also, one day, replace intestinal transplantation and could solve the problem of donor shortages.

Without enough intestinal length, babies are dependent on intravenous feeding, which can cause liver damage.

Intestinal failure occurs in more than 24 out of 100,000 live births, with nearly a third of patients dying within five years.



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