Laboratory-grown “mini bile ducts” first used in regenerative medicine to repair the human liver

Scientists have shown that they can use techniques to grow bile duct organoids, often referred to as “mini-organoids” in the laboratory, to repair damaged human livers. This is the first time this technology has been used on human organs.

This study paves the way for cell therapy to treat liver disease. That is, growing a mini-bile duct in the laboratory as a replacement part that can be used to restore the patient’s own liver to health, or to repair the liver of a damaged organ donor. That they can still be used for transplantation.

The bile ducts act as a waste treatment system for the liver, and dysfunctional bile ducts are behind one-third of adults and 70% of liver transplants in children without alternative treatment. Currently, there is a shortage of liver donors. According to the NHS, the average waiting time for liver transplants in the UK is 135 days for adults and 73 days for children. This means that only a limited number of patients can benefit from this treatment.

There is an urgent need for an approach to increase the availability of organs or to provide an alternative to whole organ transplantation. Cell-based therapies may offer advantageous alternatives. However, the development of these new therapies is often compromised and delayed due to the lack of a suitable model for testing safety and efficacy in humans before embarking on clinical trials.

Now, Studies published in Science, Cambridge University scientists said recentlyPerfusion system“It can be used to maintain the donated organs outside the body. This technique can be used to transplant and repair bile cells grown in the laboratory known as bile duct cells into the damaged human liver. -For the first time, they have repaired livers that appear unsuitable for transplantation due to bile duct damage.-In principle, this approach is to accelerate the clinical application of cell-based therapies. , Applicable to various organs and diseases.

“Given the chronic shortage of donor organs, it is important to consider ways to repair damaged organs, or even provide alternatives to organ transplantation,” said the Welcome-MRC Cambridge Stem Cell Study. Fotios Sampaziotis of the place says. “We’ve been using organoids for years to understand biology, disease, or the ability of small animals to regenerate, but we’ve always wanted to be able to use them to repair damaged human tissue. Our study is, in principle, the first study to show that this should be possible. “

Bile duct disease affects only one tube, not the other. This is important because in disease, the ducts that need repair are often completely destroyed, and bile duct cells can only be successfully harvested from spare ducts.

Researchers use single-cell RNA sequencing and organoid culture techniques to transform bile duct cells from the gallbladder, which are normally immune to disease, into bile duct cells that are normally destroyed, although the duct cells differ. I discovered that it could be done. Using a component of bile known as bile acid, the disease (intrahepatic tract) and vice versa. This means that the patient’s own cells from the less diseased area can be used to repair the destroyed tube.

To test this hypothesis, researchers grew gallbladder cells as organoids in the laboratory. Organoids are clusters of cells that can grow and proliferate in culture and have a 3D structure with the same tissue structure, function, gene expression, and gene function as some of the organs under study. Next, they transplanted these gallbladder organoids into mice and discovered that they could actually repair damaged tubes, paving the way for regenerative medicine applications in the context of diseases affecting the bile system.

The team used this technique on the liver of a human donor, leveraging the perfusion system used by researchers based at Addenbrooke’s Hospital. They injected gallbladder organoids into the human liver and showed for the first time that the transplanted organoids repaired organ ducts and restored function. Therefore, this study confirmed that those cell-based therapies could be used to repair damaged liver.

“This is the first time we have been able to show that cells grown in the laboratory can be used to strengthen or repair the human liver. Further work is done to test the safety and feasibility of this approach. We need to do this, but we hope we can move it to the clinic in the next few years. ” Wellcome-Ludovic Vallier, co-author of the MRC Cambridge Stem Cell Institute.

Researchers hope that this approach will be used to repair the patient’s own liver, but it also provides a potential way to repair a damaged donor liver and is considered suitable for transplantation. I am.

“This is an important step in enabling the use of organs that were previously considered unsuitable for transplantation. In the future, it may help reduce pressure on the waiting list for transplantation. “. Kourosh Saeb-Parsy and co-author of the University of Cambridge.

Reissued by courtesy of the University of Cambridge. Photo: Regenerating the human liver can reduce the waiting time for a transplant.Credit: University of Cambridge