NIHR-supported researchers have demonstrated that a new technique to grow ‘mini bile ducts’ in a lab can be used to repair damaged human donor livers. In the future this new technique could potentially help treat patients whose own livers are not functioning correctly. Bile ducts act as the liver’s waste disposal system. Malfunctioning bile ducts are behind a third of adults and 70% of children’s liver transplantations, with no alternative treatments. Even after a liver transplant, bile duct disease can still occur.
The disease can return in up to a third of patients after transplantation. Currently there is a shortage of liver donors. Many livers are unsuitable for transplant due to a number of reasons, such as the organ sustaining damage while being held in cold storage outside the body.
With the shortage of livers, researchers wanted to find an alternative treatment to see if the liver could instead be repaired. Researchers supported by NIHR Cambridge Biomedical Research Centre have used a technique to grow bile duct organoids – often referred to as ‘mini organs’ – in the lab and have shown that these can be used in Repair of Damaged Human Donor Livers.
This is the first time that the technique has been used on human organs.Researchers have been able to show that it is possible to transplant cells grown in the lab known as cholangiocytes organoids – which in the bile duct that act as a barrier between the bile and other tissues – into damaged human livers to repair them.
The research team used a technique known as single-cell RNA sequencing to learn more about the individual cells lining the biliary tree. They found that although duct cells differ, biliary cells from the gallbladder, which are usually spared by bile duct diseases, could be converted into the cells of the bile ducts and replace and repair the damaged ones.
They grew cholangiocytes from the gallbladder using a technology known as ‘organoids’ – small groups of cells that mimic the organ’s function – in the lab. And using the perfusion system, the researchers injected these organoids into a damaged donor liver.
The team were able to demonstrate that the transplanted organoids engrafted and repaired the bile ducts, allowing the liver to function correctly. This new technique has shown that a cell-based therapy could help restore damaged donor livers and may have the potential to fix a patient’s own liver.
This is the first time that a procedure of this kind has been used on human donor organs. It could also increase the number of livers that are considered suitable for organ transplantation and ultimately save more lives.
The research provides a proof-of-principle for the development of new cell-based therapies and this approach could be applied to a range of organs and diseases to accelerate more cell-based therapy research.
Professor Ludovic Vallier, theme lead for Transplant and Regenerative Medicine theme at NIHR Cambridge BRC and joint senior author of this study, said: “This is the first time that we’ve been able to show that a human liver can be enhanced or repaired using cells grown in the lab.
We have further work to do to test the safety and viability of this approach, but hope we will be able to transfer this into the clinic in the coming years.