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11 March 2002

Liver regeneration: the emergence of new pathways.

Artur Zimmermann

Med Sci Monit 2002; 8(3): RA53-63 :: ID: 420896


The present overview summarizes important knowledge having accumulatedduring the last years. The liver maintains a steady mass which is basically controlled by a delicatebalance between cell gain and cell loss. However, reconstitution of the organ after tissue loss doesnot only involve replacement of target cells, but also complex remodeling processes resulting in thereconstruction of the typical tissue architecture. Most information in liver regeneration refers to hepatocytes.It is important to note that hepatocytes are not terminally differentiated cells, but cells situatedin the G0 phase that can undergo proliferation upon appropriate stimulation. In most situations, hepaticstem cells are not significantly involved in this response. Hepatocyte regeneration is accomplished bya sequence of distinct phases: an initiation phase, rendering cells in a state of replicative competence;a proliferation phase, where expansion of the cell population occurs; and a termination phase, wherecell growth is suppressed to terminate regeneration at a set point. These three phases are regulatedby a whole group of factors, mainly cytokines, the significance of which has in part been defined byuse of animal models with target gene deletions (gene knockouts). It seems that several mechanisms arecapable to sense the critical cell mass which has to be achieved. Hepatocyte regeneration is accompaniedby a complex remodeling of hepatic tissue, with a transient breakdown of the lobular architecture. Incontrast to hepatocytes, less is known for the the regenerative replacement of bile ducts, blood vesselsand hepatic stellate cells.

Keywords: Cell Division, G0 Phase, Hepatocytes, Liver, Liver Diseases, Regeneration

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750