Stem and Progenitor Cells and Functional Activity of the Liver of Wistar Rats of Different Ages

Rationale and Objectives: The liver has a huge potential for self-regeneration, but with age the activity of regeneration processes decreases. Among others, changes in the functional activity of various liver cell populations take place, and studies on these changes can form the basis for the development of new therapeutic approaches to liver diseases in the elderly. The aim of the work was to study the differences in the contents of stem and progenitor cells and the functional activity of the liver of rats of different ages. Materials and methods: Wistar rats aged 6 and 12 months were used in experiments. Morphological changes were assessed by ultrasonic and histological examination of the liver. The lipid spectrum of blood serum was determined by biochemical methods. The surface and intracellular antigens of stem and progenitor cells isolated from the bone marrow, arterial blood, and liver of rats were studied by cytometric methods. Results and discussion: In 12-month-old male Wistar rats, unlike 6-month-old ones, excessive formation of extracellular matrix components, disruption of tissue architecture, development of portal hypertension, and increased concentrations of cholesterol, triglycerides, and high- and low-density lipoproteins were revealed. Statistically significant age-related differences in the contents of hematopoietic and mesenchymal stem cells, epithelial cells (CD45–CD326+) in the bone marrow, blood, and liver were observed. In the liver parenchyma of 12-month-old rats, the populations of bipotent hepatocyte precursors (CD45–CD326+CD133+) and oval cells (CD45–CD326+CD133+CD90+) were statistically much lower than in 6-month-old animals. At the same time, in the rat liver parenchyma, the total population of cells that expressed the intracellular marker Sox9 was statistically significantly higher in 1-year-old animals compared to younger animals, whatever the cell phenotype. Conclusions: In the liver of 12-month-old rats, compared to 6-month-old rats, the number of cells expressing Sox9 and lymphocytes with an inflammatory phenotype increases, the number of stem cells and various populations of epithelial and endothelial cells decreases, which adversely affects the regenerative capacity of the liver destroys the tissue architecture of the organ, and changes the lipid metabolism. These changes are largely responsible for the enhanced predisposition to chronic liver diseases at an older age.