Biliary Organoids Successfully Transplanted into Mice

Artificial human bile ducts have been grown and transplanted into mice by MRC-funded scientists, paving the way for future treatment of childhood liver diseases.

The University of Cambridge researchers took healthy cells from bile ducts, called cholangiocytes, and grew these into functioning 3D duct structures known as biliary organoids. When transplanted into mice, the scientists observed that the organoids assembled themselves into bile duct-like structures.

Collaborating with colleagues in the university’s engineering department, the team then tested whether the biliary organoids could be grown on a 3D structure made from collagen (a natural substance in the body) which could be shaped into a tube. After 4 weeks, the cells had fully covered the miniature scaffolding, resulting in artificial tubes with the main features of a normal, functioning bile duct. These artificial ducts were then successfully used to replace damaged bile ducts in mice.

Bile duct disorders are the leading cause for liver transplantation in children. This pioneering research shows that it is possible to generate and transplant human artificial bile ducts, offering hope for the future treatment of life-threatening childhood diseases such as biliary atresia.

The research was led by Professor Ludovic Vallier and Dr Fotios Sampaziotis from the Wellcome – MRC Cambridge Stem Cell Institute and Dr Kourosh Saeb-Parsy from the University of Cambridge.

Dr Sampaziotis commented: “The capacity of these cholangiocyte organoids to grow successfully on biodegradable scaffolds, organise into functional cells and rescue bile duct function illustrates the power of tissue engineering and regenerative medicine.”

Dr Rob Buckle, Chief Science Officer at the MRC added: “These research findings pave the way for exciting new regenerative medicine treatments for this life-threatening childhood liver disease. The approach to engineering replacement tissue is also likely to have impact for many other disorders. The long-term support provided to the stem cell institute by the MRC and Wellcome enables such scientific advances to flourish in an interdisciplinary environment that is geared towards the development work needed to bring health benefits to the community.”

This article has been republished from materials provided by MRC. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Sampaziotis, F., Justin, A. W., Tysoe, O. C., Sawiak, S., Godfrey, E. M., Upponi, S. S., . . . Vallier, L. (2017). Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids. Nature Medicine. doi:10.1038/nm.4360