Scientists from Cincinnati Children’s Hospital Medical Center and their collaborators have used human stem cells to develop liver organoids that faithfully replicate key zones observed in human livers. Furthermore, when the organoids were transplanted into immunodeficient rats whose liver-bile duct systems had been disconnected, their survival rates nearly doubled. Details are published in a new Nature paper aptly titled, “Multi-zonal liver organoids from human pluripotent stem cells.”
Organoids that faithfully replicate the human liver are an essential tool for scientists who study the organ’s biology and disease. “There [is] outstanding hepatocyte diversity and associated functional orchestrations in the human liver that do not exist in rodents,” said Takanori Takebe, MD, PhD, the study’s corresponding author. “This new system paves the way for studying, and eventually treating, a wide range of otherwise fatal liver disorders.”
The paper provides details on how the new organoids were developed, and how they function—including data from single-cell RNA sequencing. More research is needed to fully understand how the organoids match up with natural human organ development. Additionally, the scientists are working to develop chemical methods for triggering zonal development in the new organoids rather than relying on gene editing. This would make it more practical to study disease development and drug responses at a personal level.
In the short term, these multi-zonal liver organoids will help scientists shed new light on diseases like diabetes, drug-induced liver injury, alcohol-related liver disease, and viral hepatitis. And it could also help accelerate the development of therapies that restore liver health. For example, the organoids could be used to study and make more accurate predictions about drug metabolism and toxicity in humans.
Longer-term, for people on waiting lists for liver transplantation, this study moves the scientific community one step closer to “growing” replacement organs using patients’ own tissue instead of relying on organ donation. Currently, more than 9,000 Americans are registered on waiting lists to receive a liver transplant, according to the federal Organ Procurement and Transplantation Network. Every year, an estimated 2,000 people die on waiting lists, while far more people never become eligible.
With these results, “we have taken a significant step forward at growing liver tissue in the lab that accurately mimic[s] human liver function,” said Aaron Zorn, PhD, co-director of Cincinnati Children’s Center for Stem Cell and Organoid Medicine. “While human liver organoid transplantation remains at least several years away, in the lab, these special tissues may help us find ways to prevent people from ever needing a liver transplant.”
