Bile Duct Organoids as an Approach to Liver Repair
As Lygenesis is in the process of demonstrating, transplantation of functional liver tissue in the form of lab-grown organoids can restore enough lost liver function to make a meaningful difference to patients. Lygenesis transplants into lymph nodes, while the numerous other groups engaged in the production of liver organoids are focused on adding new liver tissue directly to the existing liver. The research here is an example of the type, including a clever proof of concept study using donor organs. A sizable number of such organs are too damaged for use in transplantation. For many lines of work in tissue engineering, enabling more donor organs to be used is an early possible application, prior to direct use in patients.
Bile ducts act as the liver's waste disposal system, and malfunctioning bile ducts are behind a third of adult and 70 per cent of children's liver transplantations, with no alternative treatments. There is currently a shortage of liver donors. Approaches to increase organ availability or provide an alternative to whole organ transplantation are urgently needed. Cell-based therapies could provide an advantageous alternative. However, the development of these new therapies is often impaired and delayed by the lack of an appropriate model to test their safety and efficacy in humans before embarking in clinical trials.
Now, scientists have developed a new approach that takes advantage of a recent perfusion system that can be used to maintain donated organs outside the body. Using the techniques of single-cell RNA sequencing and organoid culture, the researchers discovered that, although duct cells differ, biliary cells from the gallbladder, which is usually spared by the disease, could be converted to the cells of the bile ducts usually destroyed in disease and vice versa using a component of bile known as bile acid. This means that the patient's own cells from disease-spared areas could be used to repair destroyed ducts.
To test this hypothesis, the researchers grew gallbladder cells as organoids in the lab. Organoids are clusters of cells that can grow and proliferate in culture, taking on a 3D structure that has the same tissue architecture, function, and gene expression as the part of the organ being studied. They then grafted these gallbladder organoids into mice and found that they were indeed able to repair damaged ducts, opening up avenues for regenerative medicine applications in the context of diseases affecting the biliary system.
The team used the technique on human donor livers taking advantage of the perfusion system. They injected the gallbladder organoids into the human liver and showed for the first time that the transplanted organoids repaired the organ's ducts and restored their function. This study therefore confirmed that their cell-based therapy could be used to repair damaged livers.