Artificial bile duct tissue could treat liver diseases and reduce the need for transplantation

Scientists from the University of Cambridge have uncovered a way to artificially grow bile ducts, research which could reduce the need for transplant surgery and save children from life-threatening liver diseases.

Bile ducts are tube-like structures which transport bile, a fluid vital to the digestion of food, from the liver. If these ducts stop working properly, for example through obstruction, then this can lead to a range of different liver diseases, such as the childhood disease biliary atresia.

Currently, the only way to treat such diseases is by transplantation surgery, where tissue is taken from a donor and introduced into the patient to reconstruct or repair damaged bile ducts. The problem is that a lack of available donor tissue has resulted is a lack of treatment options for patients suffering from these disorders.

However new research, which has been published in the journal Nature Medicine, could provide hope for this medical area as researchers demonstrate that growing healthy, transplantable bile duct tissue in the lab is entirely possible.

“Our work has the potential to transform the treatment of bile duct disorders,” said Professor Ludovic Valier, one of the lead researchers from the Wellcome-MRC Cambridge Stem Cell Institute. “At the moment, our only option is liver transplantation, so we are limited by the availability of healthy organs for transplantation. In future, we believe it will be possible to generate large quantities of bioengineered tissue that could replace diseased bile ducts and provide a powerful new therapeutic option without this reliance on organ transplants.”

The team began by isolating healthy cells from the bile duct, known as cholangiocytes. They were able to grow these cells into 3D structures called extrahepatic cholangiocyte organoids (ECOs). These ECOs still expressed important markers which are typically present in biliary tissue. Extraordinarily, when the team transplanted these 3D structures into mice, the ECOs showed the ability to self-organise into bile duct-like tubes.

The scientists then found the ECOs could be grown on special biodegradable scaffolds which are used in reconstructive surgery to provide structure and support for tissue. When these scaffold / ECO combinations were introduced into mice with defective gall bladders, they were able to successfully repair the damaged tissue.

To test the ability of these organoids to replace bile ducts, the cells were grown on a scaffold which was then transplanted into mice with damaged ducts. After four weeks, the cells had completely grown, and normal duct function was restored.

The rapid growth of the cells could help to address the urgent need for tissue in patients affected by bile duct disorders. What’s more, the relative ease and speed of their growth could help drive research to better understand these diseases; research being previously hindered by the limited ability of scientists to grow and culture the necessary cells.

“This demonstrates the power of tissue engineering and regenerative medicine,” said Dr. Fotios Sampaziotis, a member of the research team. “These artificial bile ducts will not only be useful for transplanting, but could also be used to model other diseases of the bile duct and potentially develop and test new drug treatments.”