Introduction: In many human organs, the rate of cell turnover in healthy and pathological conditions remains mostly unknown. This is mainly because it is challenging to research this process in humans. Although the liver has a remarkable ability to regenerate following partial hepatectomy, little is known about how hepatocytes are replaced to maintain homeostasis. Hepatocytes can develop multiple nuclei and polyploidy. It is unknown what causes polyploidy and whether it has any biological advantages for health and sickness. Due to the liver's amazing propensity for cell proliferation, it may repair itself after harm by producing new, functional tissue. Due to methodological limitations, there hasn't been a thorough investigation defining the dynamics of human hepatocyte turnover, including their age distribution and the effects on hepatocyte functionality in the aging liver. Establishing these aspects of adult liver cell regeneration is crucial, particularly to better understand age-related illnesses and the emergence of liver cancer. Consequently, we want to describe human hepatocyte turnover using retroactive birth dates.
Methods: In this study, we will use computational image analysis to quantify the distribution of nuclear ploidy and multinucleation in human hepatocytes and to ascertain the turnover dynamics of various ploidy levels in hepatocytes. By detecting the quantities of 14C, a byproduct of Cold War nuclear bomb tests, in the genomic DNA of flow cytometry-isolated hepatocyte nuclei with various ploidy levels, one may determine the dynamics of turnover. These investigations might serve as the foundation for therapeutic plans that target pharmacologically controlling hepatocyte renewal to enhance liver function in severe liver disease.
Results: In the current experiment, we were able to corroborate earlier findings that indicated polyploid hepatocytes renew at a slower rate than diploid hepatocytes due to differences in their 14C contents. Although some rodent research appears to confirm this theory, other rodent studies reveal a proliferative potential that is unaffected by the ploidy level of hepatocytes. It is difficult to compare hepatocyte regeneration across mice and humans because of their differing ploidy profiles.
Conclusion: Retrospective birth date using 14C shows that the human liver is still a young organ even in the elderly. We saw a continuous and significant turnover of hepatocytes over the course of the lifetime, which is closely related to the ploidy level. In comparison to polyploid hepatocytes, diploid hepatocytes have an eight-fold higher yearly renewal rate. In humans, exchange between ploidy classes barely affects liver homeostasis. An essential topic that needs to be answered is whether long-lived polyploid cells render the liver more vulnerable to age-related disorders or whether they work as a resilience element to deal with cellular stress, preventing organ function loss and cancer. In conclusion, rodents are largely used to study the liver, a complicated organ with a population of hepatocytes that is highly heterogeneous. The current thesis identified variations in the turnover rates of the various ploidy classes of human hepatocytes. Additionally, we discovered early evidence that metabolic liver zonation affects polyploidy, which in turn affects cell cycle activity and may affect hepatocyte regeneration. To provide a complete picture of liver cell renewal, future studies must look into these consequences.