Uncovering the Molecular Mechanisms Underlying Liver Regeneration

Using clinical samples, researchers from the University of Leipzig Medical Center, the Max Planck Institute for Evolutionary Anthropology, TU Dresden, and ETH Zurich have examined the changes in liver cell types before and following regeneration.

This study was published in the journal Nature Communications, and they produced a cell atlas.

Portal Vein Embolization (PVE), a well-established treatment, initiates liver regeneration in clinical practice. It is especially useful to restore liver function in people who have liver tumors or other illnesses of the liver after portions of the tissue have been surgically removed.

The portal vein, which supplies blood to certain liver parts, is blocked during this treatment. As a result, blood flows through other organ segments with greater force. The liver segments that are well-circulated grow, whereas the segments that are obstructed decrease.

In certain liver surgery situations at the University of Leipzig Medical Center, radiological technology is used to embolize the portal vein to start the regeneration of a liver lobe before surgical intervention.

Following PVE, tissue samples from patients were obtained for the current investigation. Around 9,400 cell nuclei and about 21,000 cells were examined.

By identifying cell types using advanced analytical methods, we have been able to create a cell atlas of the healthy human liver. Our research makes a valuable contribution to the field of hepatology to better understand human diseases such as fibrosis, cirrhosis, and the development of liver cancer.”

Dr. Georg Damm, Study Corresponding Author and Research Laboratory Head, Visceral, Transplantation, Thoracic, and Vascular Surgery, University of Leipzig

The cell atlas is a map set that classifies a tissue's cell types based on variations in their active genes. Comparing the maps of healthy and regenerating liver tissue reveals that the liver exhibits an increase in genes linked to cellular adhesion, inflammation, and developmental processes.

Additionally, the researchers discovered that the design of the liver's smallest structural units, liver epithelial cells, changes from the portal vein to the central vein. This change is essential to the liver's metabolic processes.

Additionally, alterations in the makeup of immunological and vascular cell subtypes were noted, which may indicate a sophisticated and dynamic liver tissue response. This study's examination of the interactions between various types of liver cells demonstrates that connective tissue cells serve as a central point for interactions between vascular and immune cells.

It also emphasizes the significance of intercellular proteins for human liver regeneration.

Capturing the dynamic changes that occur in this regeneration model opens up new possibilities for future therapeutic interventions. The new data provide a rich source for studying cellular and histological changes in human liver regeneration. In follow-up studies, we want to shed more light on individual mechanisms and further validate them in human models.”

Daniel Seehofer, Professor, Hepatobiliary and Transplant Surgery, University of Leipzig

Seehofer is also the Head of the Department of Visceral, Transplant, Thoracic, and Vascular Surgery at the University of Leipzig Medical Center.