Is this the modern Heracles? Unravelling the potential of liver organoids to study rare liver diseases in children
Currently, there are limited or no therapies available for many children affected by rare liver diseases. Liver transplantation is often their only hope. With the development of liver organoids, doctors and patients were given new hope for the development of personalized treatments for rare liver diseases. Yet, little was known about the potential of liver organoids in personalized medicine. Hence, Vivian Lehmann spent her PhD researching the use of liver organoids to study mechanisms and potential therapies for rare liver diseases and defended her work on the 30th of November 2023.
The results showed that liver organoids indeed reflect the symptoms of for example Cystic fibrosis, PFIC2 and Wilson disease patients. However, it also became clear that several other diseases cannot be studied with these organoids. It seemed that the liver organoids showed some characteristics of the major cell type of the liver, the hepatocyte, but also some of cholangiocytes, which line the bile ducts.
Liver organoids to study diseases affecting the bile ducts
With these hybrid cells in hand, Vivian and her colleagues explored whether liver organoids would be useful to study biliary atresia (BA). Patients with BA are born with occluded bile ducts and require correction surgery within the first few months of life. While the exact cause and mechanism behind BA remains elusive, cholangiocytes have been thought to play a key role in BA development. Hence, Vivian set out to characterize BA patient liver organoids and challenge them with toxins and viruses which are thought to be involved in BA development.
The results suggest that liver organoids of BA patients indeed behave differently than those of healthy donors under normal conditions and when challenged with a virus. These results are very exciting and suggest that liver organoids can aid in unraveling the disease mechanism behind BA.
Making liver organoids more hepatocyte-like
Since the traditional culture technique seemed insufficient to provoke mature hepatocyte characteristics, Vivian and her colleagues developed a novel culture system. The organoids were grown on narrow hollow tubes made of woven fibers. When coating the tubes with Matrigel or synthetic laminins key hepatocyte characteristics were improved in the liver organoid cells. Following this great leap forward, Vivian’s colleagues are now continuing to test medications with this system and connect the liver-on-a-tube to other organ systems to study multi-organ effects of such drugs.
The next step
Since the start of her PhD in 2019, Vivian has been involved in many science communication projects. Although she loved to see her organoids grow, the bigger picture of a project and communicating science stories to the wider public lies closer to her heart. Hence, Vivian is stepping out of the lab and will start at NWO as a project officer and science communicator in 2024.