New bile ducts grown in a dish

08 July 2017
Posted by Chris Smith.

Scientists in Cambridge have developed a new technique to grow replacement bile ducts for patients with liver disease.

Some children are born with a defective or blocked bile duct, and some adults develop diseases affecting the bile duct system later in life. In both cases the results can be lethal, and even require a transplant, if the condition isn't treated.

Now, writing in Nature Medicine, Cambridge University liver specialist Fotios Sampaziotis and his colleagues describe a technique for growing new bile-duct tissues in the culture dish.

Transplanted into mice in place of the animals' native bile ducts, the Cambridge team's bio-engineered grafts remained viable and the animals survived with normal liver function.

The bile duct connects the liver, where bile is made, to the intestine. Bile helps in the digestion of fats, but if it cannot escape from the liver it builds up and eventually poisons liver cells, causing patients to become jaundiced.

This is what happens to children with a birth defect called primary biliary atresia, which would be directly amenable to being treated using the technique pioneered by Sampaziotis and his co-workers.

Their approach was first to take cells from the lining of the bile duct, or the gallbladder.

These cells, known as cholangiocytes, are highly specialised at resisting the toxic effects of bile.

By incubating them in the right culture conditions, specifically using three-dimensional gel culture systems, the cells could be persuaded to proliferate, retain their bile-resistant characteristics and stick onto a bio-compatible scaffolding material that could be used to produce a bile duct patch or even a new tubular bile duct.

"And these cells would come from the patient himself," says Sampaziotis, meaning that the tissue would be immune-compatible with the recipient. "Obviously this was just in mice, but it gives us confidence that this should work."

The present work deals only with how to repair bile duct problems outside the liver. But, according to Sampaziotis, they are now considering the next step, which is how to carry out bile duct repairs inside the liver itself.

"That's really important, because we cannot do this surgically, and lots of adults have liver problems caused by bile duct disease. So instead we may have to go in via the intestine and inject new cells up the bile duct itself to replace the damaged or defective cells upstream."

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