Liver regeneration

Abstract

The liver is unique in its ability to regenerate in response to injury. A number of evolutionary safeguards have allowed the liver to continue to perform its complex functions despite significant injury. Increased understanding of the regenerative process has significant benefit in the treatment of liver failure. Furthermore, understanding of liver regeneration may shed light on the development of cancer within the cirrhotic liver. This review provides an overview of the models of study currently used in liver regeneration, the molecular basis of liver regeneration, and the role of liver progenitor cells in regeneration of the liver. Specific focus is placed on clinical applications of current knowledge in liver regeneration, including small-for-size liver transplant. Furthermore, cutting-edge topics in liver regeneration, including in vivo animal models for xenogeneic human hepatocyte expansion and the use of decellularized liver matrices as a 3-dimensional scaffold for liver repopulation, are proposed. Unfortunately, despite 50 years of intense study, many gaps remain in the scientific understanding of liver regeneration.

Figure 1. Multi-hit hypothesis of Drug-Induced Acute Liver Injury

Acute injury to hepatocytes by hepatotoxic drugs such as D-galactosamine and acetaminophen reduces their functional capacity leading to an accumulation of waste products such as ammonia in the blood. Acute liver injury is also associated with the release of proinflammatory cytokines from the liver which have local adverse effects on hepatocytes leading to their impaired mitosis and extrahepatic effects such as systemic inflammation. The combination of waste molecules and proinflammatory cytokines systemically are believed to impair function of kidneys and lungs, and lead to edema formation in the brain. These systemic manifestations of acute liver failure are frequent causes of death in humans. (ECM, Extracellular Matrix)