Stem cell transplants offer hope for sufferers of gut disorders

A Melbourne research team has successfully transplanted stem cells into the muscles of the bowel, offering hope of one day restoring bowel function in children with severe and distressing gut disorders such as Hirschsprung’s Disease, for which there are few current effective treatments.

Babies with Hirschsprung’s are born without the nerves needed for peristalsis — the muscular contractions that push food from the oesophagus to the anus.

It is usually diagnosed at birth when they fail to pass their first stool, or meconium. The only current treatment is surgery, and lifelong complications and psychosocial problems are common.

The gut has its own nervous system — often dubbed ‘the second brain’ — laid down before birth.

Neural stem cells migrate from the base of the brain to the gut. They are then supposed to differentiate into neurons that control various aspects of the digestive process — but some cells go missing in action.

A research team led by Professor Heather Young and Dr Lincon Stamp set out to complete that migratory journey, using stem cells in mouse models.

“We found that as little as one month after transplantion, the stem cells didn’t just look like neurons— they were behaving like proper neurons,” Dr Stamp said.

The team used a technique called optogenetics, using light to activate the neurons and then record their activity within the muscle walls.

“We found these neurons weren’t just firing off signals, but were also connecting with the bowel wall.”

Professor Young said that, in humans, it has been shown that stem cells persist even into adulthood in healthy parts of the bowel.

“We hope that these ‘long-life’ stem cells might provide a source of patient-derived cells, which could be grown outside the body and then returned to the defective bowel to restore its function,” she said.

The research, published in the journal Gastroenterology, may also provide useful insights for gut disorders affecting adults, such as:

• gastroparesis, an increasingly common condition often associated with diabetes, in which the stomach has trouble emptying, and
• achalasia, in which the neurons regulating the oesophagal sphincter instead keep it closed, causing choking and an inability to keep down food.

The NHMRC-funded project is a collaboration between the Departments of Anatomy and Neuroscience and Physiology at the University of Melbourne, and the Florey Institute for Neuroscience and Mental Health. Read the full story on Pursuit