Local scientists here have successfully created human liver organoids, or “mini livers”, to help them develop and trial therapies for various liver diseases.
This is part of a research collaboration between the Agency for Science, Technology and Research’s Genome Institute of Singapore (GIS) and the National University of Singapore (NUS). The liver organoids, each with a diameter of around 0.5mm, are able to capture the functional and structural features of the human liver.
Cultivated in vitro in a petri dish, the organoids are grown outside the body from stem cells, which are initially reprogrammed from human skin cells over a three-month period.
To better understand the effects of non-alcoholic fatty liver disease (NAFLD) on the organ, the liver organoid cells are supplemented with a fatty acid-rich nutrient, to replicate the effect of high carbohydrate and fatty food intake, which is said to be the primary cause of the disease.
Characterised by the building up of fat in the livers of people who consume little to no alcohol, the disease is often associated with obesity and Type 2 diabetes, affecting up to a third of the local adult population.
When fatty food is consumed, hepatocytes, which make up around 80 per cent of the cells within the liver, help to store and process excess fats.
Cholesterol from these fats are then secreted into liver canals known as the bile canaliculi, before reaching the gastrointestinal system where it is absorbed into the blood.
However, too much fat being accumulated in the liver may result in disruptions to the structure and function of the hepatocyte cells, while the bile canaliculi may end up being shortened or diminished.
When combined, this could lead to liver injury, eventually hampering the organ’s function over time.
In more severe cases, the disease could lead to liver cancer and liver cirrhosis, where the liver no longer functions properly, owing to long-term damage.
Liver organoids developing in a dish (far left) and a visualisation of different cell types and liver structures in the organoids, including hepatocyte cells and bile canaliculi (both in green). PHOTO: GENOME INSTITUTE OF SINGAPORE
Associate Professor Dan Yock Young of NUS’ Yong Loo Lin School of Medicine said: “Patients with early stage NAFLD remain largely asymptomatic, and the disease progresses silently over the years.
“What drives the disease progression and liver injury remains largely unknown. The development of advanced human liver models of the disease will provide a critical tool for researchers to identify molecular drivers of the disease.”
Through the liver organoid model, scientists can observe and capture molecular and structural changes of the liver as the disease progresses – all within the course of a week.
In addition, the organoid model could also serve as a useful tool for drug testing and screening, given that there are currently no approved therapies for NAFLD.
As the disease is closely associated with obesity, the treatment recommendations for patients with liver disease are often dietary and lifestyle changes.
Professor Ng Huck Hui, senior group leader at GIS, said: “The increase in prevalence of liver disease and the lack of therapeutics place a huge burden on healthcare systems worldwide.
“There is a dire need to better understand liver biology in order to develop advanced cellular models of disease, and novel therapies.”