Fatty liver disease, now called metabolic dysfunction-associated steatotic liver disease (MASLD), is one of the most common chronic liver conditions worldwide. If left untreated, it can lead to liver scarring (fibrosis), cirrhosis, or even liver cancer. Despite its serious impact, there are still no effective treatments. This PhD research of Junyu Wang aimed to better understand how liver cells “talk” to each other during the development of MASLD and scarring, and how we might use that knowledge to find new treatment approaches.
The first part of this work focused on extracellular vesicles (EVs)-tiny, bubble-like messengers released by cells to carry information. By studying EVs exchanged between different types of liver cells, such as endothelial cells, stellate cells, immune cells, and hepatocytes, we discovered that some EVs can reduce inflammation or prevent scar formation, while others may worsen the disease.
In the second part, we used hydrogels made from real liver tissue, which mimic the liver’s natural environment in the lab. These liver ECM (L-ECM) hydrogels improved the survival and function of liver cells outside the body. Interestingly, the stiffness of these gels also influenced whether cells became more or less likely to contribute to scarring.
Together, these findings provide new insight into how the liver’s environment and internal cell communication drive disease progression. The research may pave the way for future therapies based on EVs and help create better laboratory models for testing treatments. In the long term, this knowledge could support more personalized approaches to prevent or reverse fatty liver disease.
Junyu Wang is part of MoHAD.
