Dynamics of disease progression and regeneration in a multiscale liver model

With a rising prevalence of lifestyle-associated diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD), the liver represents a focal point of medical research. As the central metabolic organ, the liver orchestrates carbohydrate, lipid and amino acid signaling and maintains energy homeostasis. Metabolic changes in response to obesity contribute to steatotic liver disease and liver cancer development. However, the complexity of the signaling networks involved and the plethora of factors affecting the liver, e.g. sex and diet, require a systems biology approach to investigate disease progression, regeneration, and possible therapeutic intervention points.

Murine and human liver samples with varying degrees of liver steatosis were analyzed using 2D and 3D immunofluorescent imaging and integrated into a multiscale 3D liver model. Additionally, transcriptomic and proteomic data of murine liver provides a basis for identification of candidate pathways and therapeutic targets in humans.

The study revealed the impact of sexual dimorphism dynamics of steatosis. In mice, proliferation, regeneration and cellular respiration are modulated in a sex-dependent manner. Additionally, a multiscale model showed morphological and architectural changes in the liver parenchyma.

The presented results demonstrate the interplay of sex difference, disease progression and regenerative capacity in the murine liver. Ongoing human parameterization and refinement of a dynamic multiscale model will aid with the prediction of liver disease progression, providing an important step in liver cancer prevention.

Publication History

Article published online:
20 January 2025