The results of an important study published in the scientific journal Cell Reports describe the development of a new model capable of reconstructing key physiological features of the human liver, allowing the pathological processes that drive liver degeneration to be closely observed in the laboratory.
The study, supported by AIRC Foundation for Cancer Research, has been coordinated by Giovanni Sorrentino, Group Leader, Advanced Disease Models at ICGEB, and Associate Professor of Histology at the University of Trieste, and comprises a multidisciplinary team including biotechnologists, physicists, and clinicians, to integrate cellular biology, genomics, tissue engineering, and direct clinical observations to develop the unique research platform.
“The new system makes it possible to recreate the pathological activation of liver stem cells in the laboratory,” says Sorrentino, an expert in in vitro tissue engineering based on stem cell technologies and three-dimensional organoids. “In the early stages of chronic liver disease, this process has regenerative purposes. However, when it persists, it becomes one of the main factors in inflammation, tissue scarring, and progression toward advanced liver disease, including liver cancer.”
For the first time, the model developed by researchers allows the observation of the pathological processes that drive liver tissue degeneration in chronic diseases and tumour progression in a three-dimensional environment that faithfully reproduces the complexity of the human liver, preserving the interactions between different cell populations.
The researchers have discovered that reactive stem cell populations are critically dependent on their ability to synthesise cholesterol. Drugs widely used in clinical practice to lower cholesterol (such as statins) can halt the process of blocking abnormal stem cell activation, reducing inflammation and significantly slowing disease progression in chronic liver diseases.
“In recent years,” comments Sorrentino, “clinical data from large patient populations have shown that people taking statins for the treatment of cardiovascular disease also show a slowdown in the progression of chronic liver diseases and a reduced risk of developing liver tumours such as cholangiocarcinoma, which results from prolonged abnormal activation of stem cells.” This study could reveal the molecular mechanisms underlying this connection, explaining why statins exert a protective effect.
Beatrice Anfuso, Suresh Velnati, and Davide Selvestrel, the study’s lead authors, confirm that these results represent a decisive step forward. Thanks to the diverse expertise of team members, it has been possible to develop a platform that clarifies how the disease manifests itself and also reveals its initial vulnerabilities. The fact that one of these vulnerabilities can be treated with already approved drugs makes the discovery promising for early therapeutic intervention and disease prevention.
Link to the publication: An organotypic model of ducular reaction reveals a mevalonate-dependent vulnerability in reactive biliary cells
