Damage to the bile ducts in the liver is a common reason people need a liver transplant. Researchers have now grown functional bile ducts from human bile cells in the laboratory. This enabled them to repair a damaged donor liver that could not be transplanted. Using mice, they also showed that the replacement parts from the laboratory are also able to repair damage to the bile ducts in the living organism. Accordingly, the technology could possibly offer an alternative to liver transplants in the future. It also has the potential to make more donor livers available for transplants.
The liver produces bile and carries it through the bile ducts to the intestine, where it helps digest fats. Malfunction of the bile ducts can lead to bile buildup in the liver and ultimately liver failure. Often times, the only way out is a liver transplant. But the waiting lists for donor organs are long. Much research therefore revolves around finding alternatives to transplants or increasing the number of available donor livers.
Organoids for cell therapy
A team led by Fotios Sampaziotis from the University of Cambridge has now investigated an approach that could serve both goals. To do this, the researchers grew so-called organoids from human biliary cells. Organoids, often referred to as “mini organs”, are tiny three-dimensional organ structures that can be grown from body cells in the laboratory under certain conditions. Their structure and function largely correspond to that of the real organ. They are used, for example, to understand disease processes at the molecular level or to test drugs.
Sampaziotis and colleagues have now explored the potential of organoids for cell therapy of organ damage. “Given the chronic shortage of donor organs, it is important to look for ways to repair damaged organs or even offer alternatives to organ transplants,” says Sampaziotis. “We have been using organoids for a number of years to understand biological mechanisms, diseases, and their ability to regenerate in small animals, but we have always hoped to use them to repair damaged human tissue. Our study is the first to show in principle that this should be possible. “
Plasticity enables healing
In mice, Sampaziotis and colleagues initially caused damage to the bile ducts. Then they injected the animals with the organoids grown in the laboratory into the bile ducts. And indeed: while untreated mice died within a few weeks, the individuals who received the organoids showed largely normal liver function and survived the following months. The researchers did not find any signs of excessive tissue growth or tumors. “Thus, the organoid transplant appears to provide the healthy cells that are required to repair the damaged epithelium and to heal the acute injury,” the researchers conclude.
Their results also demonstrated that cells from different areas of the biliary system, while different, are adaptable enough to transform into one another. This is important because with biliary tract disease, individual areas are often damaged while others, such as the gallbladder, are spared. The plasticity of the cells therefore potentially enables the patient’s own cells from healthy areas to be used to repair damaged ducts.
Repaired human donor organs
“Experiments with cell transplants in mice are extremely useful, but not always suitable for predicting therapeutic outcomes in humans,” the researchers write. Therefore, they also worked with human donor livers that were unsuitable for transplantation due to damaged bile ducts. Similar to the mice, they injected organoids from human bile cells into the damaged bile ducts and were able to restore their function in this way.
“This is the first time that we have been able to show that a human liver can be improved or repaired with cells grown in the laboratory. We still have to work to test the safety and feasibility of this approach, but we hope that we will be able to transfer this to the clinic in the coming years, ”says Sampazioti’s colleague Ludovic Vallier.
From the researchers’ point of view, the technology could on the one hand be used to spare patients a liver transplant by using organoids from the patient’s own cells to repair the damage. On the other hand, more organs could be made available for transplantation. Co-author Kourosh Saeb-Parsy says, “This is an important step that will allow us to use organs that were previously considered unsuitable for transplant. In the future, this could help ease the pressure on the transplant waiting list. “
Source: Fotios Sampaziotis (University of Cambridge) et al., Science, doi: 10.1126 / science.aaz6964