The liver is the only visceral organ that possesses the remarkable capacity to regenerate. The liver can regenerate after either surgical removal or after chemical injury. It is known that as little as 25% of the original liver mass can regenerate back to its full size. The process of regeneration in mammals is mainly compensatory growth because only the mass of the liver is replaced, not the shape. However, in lower species such as fish, both liver size and shape can be replaced.
Liver regeneration involves replication of the liver cells, mainly hepatocytes, followed by other cells such as biliary epithelial cells and sinusoidal endothelial cells. Once cell proliferation is completed, the newly divided cells undergo restructuring, angiogenesis and reformation of extracellular matrix to complete the regeneration process. Interestingly, in most cases, liver function is only partially affected during liver regeneration. Whereas certain specialized functions such as drug metabolism decrease, many other primary functions such as albumin and bile production are not substantially affected.
Two main type of models are used to study liver regeneration including surgical removal also referred to as partial hepatectomy (PHX) and chemical-induced liver damage. Whereas the mechanisms and kinetics of liver regeneration in these two models are different, many of the same signaling pathways stimulate liver regeneration in both pathways.
Liver regeneration is highly controlled process regulated by complex network on highly redundant signals. Several signaling pathways are known to stimulate regeneration in the liver including cytokines, growth factors, hormones, and nuclear receptors.
The ability for the liver to regenerate is central to liver homeostasis. Because the liver is the main site of drug detoxification, it is exposed to many chemicals in the body which may potentially induce cell death and injury. The liver can regenerate damaged tissue rapidly thereby preventing its own failure. Liver regeneration is also critical for patients of liver diseases where the partial removal of the liver due to fibrosis or tumor is a common therapy that utilizes the ability of the remaining liver to regenerate back.