13 / 11 / 2023
Testing new treatments for liver fibrosis with human liver cells
Scarring of the liver, known as liver fibrosis, is a major problem which can develop into non-alcoholic fatty liver disease. Dr Syedia Rahman has been investigating ways to prevent liver fibrosis by using lab-grown human liver cells Syedia’s techniques could replace animal experiments and bring treatments to patients sooner.
Liver fibrosis is when excess scar tissue forms in the liver. The few treatment options available can only slow down liver fibrosis, not stop or reverse it. Eventually, liver fibrosis develops into liver cirrhosis, which causes about one million deaths per year worldwide. So, there is an urgent need for effective therapies to stop liver fibrosis.
Research into the causes of liver fibrosis has often used rodents such as rats and mice. But due to substantial differences between species, there is no suitable animal model of the disease. As a result, the translation of research findings from animal experiments into treatments for humans has repeatedly failed.
We need to find new ways to study how liver fibrosis develops that are more relevant to humans, so that we can find new treatments to stop the progression of non-alcoholic fatty liver disease.
Hepatic stellate cells are the main cell type involved in liver fibrosis. In her PhD project at the FRAME Lab, Dr Syedia Rahman has been using stellate cells from liver samples donated by people with varying degrees of liver fibrosis.
When the liver is damaged, hepatic stellate cells become activated and release a molecule known as transforming growth factor β (TGFβ). TGFβ causes proteins to accumulate in the liver, leading to scar formation, fibrosis, and ultimately liver cirrhosis.
However, TGFβ is released in an inactive form which must then be activated by molecules known as integrins. Researchers believe it might be possible to block integrins to stop the activation of TGFβ in hepatic stellate cells, and ultimately prevent liver fibrosis.
In her project, Syedia measured the amount of different integrins in the stellate cells obtained from human donors. She has been able to compare the patterns and amounts of integrins in different patients with varying degrees of fibrosis. Syedia has also used these human liver cells to test integrin-blocking drugs, to determine their effect on TGFβ, and their potential as a treatment for liver fibrosis.
“Several clinical trials for the treatment of liver fibrosis have failed to reproduce the promising effects observed in rodent models. […] As my project uses human samples, new drug treatments can be developed more successfully, and these results can be better translated for patient benefit.”
Dr Syedia Rahman.
Syedia’s research could reveal new information about integrins in human liver stellate cells, which could eventually lead to new treatments to stop or even reverse liver fibrosis.
Importantly, her project has also tested the use of liver cells donated by human volunteers in research. This method could mean new drug treatments can be developed more successfully, and these results can be better translated for patient benefit. This could replace animals models as a more effective, human-relevant research approach in the future.