Stellate cells are also essential for the proper functioning of the liver

An international study published in the journal Nature and led by Columbia University in New York, with the participation of researchers from Cima, the University of Navarra Clinic, and the Hospital Clínic in Barcelona, has concluded that stellate cells in the liver are essential for the proper functioning of this organ. Until now, it was only known that they were involved in the development of liver fibrosis, a disease that consists of the progressive accumulation of scar tissue in this organ in response to injury or chronic inflammation.

Dr. Josepmaria Argemí, a specialist at the Clinic's Hepatology Unit and leader of Cima's Stress Responses andLiver Cancer in Immunotherapy group, explained that "thanks to this study, it has been possible to verify that hepatic stellate cells produce a protein called RSPO3 that contributes to maintaining proper spatial or zonal organization. The expression of this protein in stellate cells decreases in liver diseases."

The researchers have worked over the last decade combining analysis techniques in human tissues and animal models and have also used genetic engineering techniques. In the laboratory, the scientists discovered that the liver's ability to regenerate, detoxify the body, and perform other important functions was profoundly altered when these cells were removed in mice.

They have also discovered that, in contrast, when these stellate cells become overly activated—which occurs in the presence of disease—the RSPO3 protein decreases in the cells. This low level of the protein predicts a worse prognosis in patients with alcohol-related liver disease, suggesting that, under normal conditions, stellate cells are involved in protecting the liver.

According to Dr. Argemí, this study “advances our knowledge of liver physiology and provides information for the development of treatments that promote liver regeneration or recovery after injury.”

Liver fibrosis is a disease that causes a progressive accumulation of scar tissue in the liver and can lead to cirrhosis. Although this organ is capable of repairing itself if it suffers minor damage, if the injury is persistent, it can seriously affect its structure and function, which often happens if high alcohol consumption continues, or if the patient suffers from metabolic liver diseases associated with obesity or type 2 diabetes, or if undiagnosed viral liver infections persist.

Bibliographic reference: Sugimoto, A. et al (2025) Hepatic stellate cells control liver zonation, size and functions via R-spondin 3, Nature, 640, 752-779