NYC Gazette

Researchers from Columbia University and the German Cancer Center have discovered a new role for stellate cells in the liver. These star-shaped cells, previously known mainly for their involvement in liver fibrosis, also play a significant part in maintaining the liver's organization and function before they contribute to liver damage.

This finding could impact millions of people worldwide, including one-third of American adults with metabolic liver disease. Robert F. Schwabe, MD, study leader and professor at Columbia University Vagelos College of Physicians and Surgeons, stated: "Our research shows a surprising role for stellate cells in the normal liver, where they act like 'secrete bosses,' organizing its structure and instructing the work of other cells that perform the liver’s main functions, namely metabolism and detoxification."

As liver disease progresses, these cells lose their protective functions. Schwabe suggests that reprogramming diseased stellate cells to their healthy state could potentially stop liver scarring and improve function, especially for patients with advanced disease stages not helped by current therapies.

Published in Nature on March 12th, the study focused on genetically engineered mice lacking most stellate cells. The absence led to smaller livers that struggled with injury healing, drug detoxification, and metabolic regulation. Eliminating RSPO3 within these cells caused similar issues.

The researchers found declining RSPO3 levels associated with worsened conditions in patients with metabolic or alcohol-associated liver diseases. Restoring healthy stellate cell states could represent a new therapeutic approach to simultaneously reduce scarring and enhance function.

Schwabe emphasized: “A key problem in patients with metabolic liver disease is that today’s drugs only target the metabolic alterations,” adding that this approach is less effective when scarring dominates advanced stages.

Efforts are underway to increase RSPO3 levels and explore other methods to restore stellate cell health. The study involved several contributors from Columbia University, Osaka University in Japan, German Cancer Research Center, Heidelberg University, among others.

This research received support from various NIH grants as well as funding from institutions like Takeda-Columbia-NYU Alliance and Deutsche Forschungsgemeinschaft. Authors declared no competing interests.