The answer to whether liver cells undergo mitosis for regeneration is yes, but this process is highly regulated and occurs only when necessary. The liver is unique among solid internal organs because of its remarkable capacity to regrow its mass after injury or surgical removal. Its primary functions involve metabolism, filtering blood, and detoxification, requiring a population of specialized cells called hepatocytes. This ability to restore functional mass is achieved through a carefully managed process of cell division, not constant, rapid turnover like the skin or gut.
The Quiescent Nature of Hepatocytes
The default state of a hepatocyte in a healthy, intact liver is one of rest, known as the G0 phase of the cell cycle. This is a reversible state of quiescence where the cells are metabolically active and performing their functions but are not actively preparing to divide. Less than two percent of hepatocytes are typically dividing at any given time in a normal liver. Unlike many other cell types that remain permanently in the G0 phase, hepatocytes maintain the potential to re-enter the cell cycle. This capacity to switch from a resting to a dividing state is the biological baseline that makes liver regeneration possible.
The Phenomenon of Liver Regeneration
Mitosis in the liver is triggered by a loss of functional liver mass, such as following surgical removal (partial hepatectomy) or significant damage from toxins. When the remaining liver tissue can no longer meet the body’s metabolic demands, a highly coordinated regenerative response begins. This response is not the regrowth of the removed portion, but rather the enlargement and division of the remaining cells, a process called compensatory hyperplasia.
The process of regeneration is rapid, involving mature hepatocytes moving out of the G0 phase and back into the G1 phase of the cell cycle. Hepatocytes are the first cells to re-enter the cycle, undergoing one to two rounds of division to replace the lost tissue. This mechanism quickly restores the liver mass to a size proportional to the body’s needs. Importantly, this regeneration typically restores the original function and mass without forming a scar, distinguishing it from the repair process in many other organs.
Biological Controls Governing Mitosis
The shift from quiescence to proliferation is governed by a cascade of molecular signals involving both immune cells and the liver cells themselves. The initial “priming” phase is mediated by pro-inflammatory cytokines, such as Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-6 (IL-6). These cytokines are secreted by non-parenchymal cells like Kupffer cells (liver macrophages) and increase the sensitivity of the hepatocytes to growth factors, preparing them for division.
Once primed, the cells are driven through the cell cycle by mitogens, notably Hepatocyte Growth Factor (HGF) and Epidermal Growth Factor (EGF). HGF, produced by hepatic stellate cells and endothelial cells, binds to its receptor on the hepatocyte surface, initiating a signaling pathway. This pathway drives the cell through the G1 phase and into the S phase for DNA synthesis. The proliferation phase continues until the liver mass is functionally restored. The process is then halted by a “stop switch,” involving signals like Transforming Growth Factor-beta 1 (TGF-β1), which sends the cells back into the stable G0 state, preventing excessive growth.
Relevance to Disease and Medical Treatment
The liver’s mitotic ability is the foundation for several modern medical procedures, most notably living-donor liver transplantation. In this procedure, a portion of a healthy donor’s liver is removed and transplanted into the recipient. The remaining segments in both individuals regenerate to full functional capacity, allowing a small piece of tissue to regrow into a full organ, which is not possible with other solid organs.
Conversely, the loss of control over this mitotic process is a hallmark of liver cancer, or hepatocellular carcinoma. While controlled regeneration involves a coordinated start and stop signal, cancer is characterized by uncontrolled cell division and a failure to re-enter the G0 phase. Understanding the mechanisms of the “stop switch” is a major focus of research, as its failure allows malignant cells to proliferate unchecked.