الفهرس 
Introduction and aim of the work.Only 14 pages are availabe for public view
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Abstract
The liver has a remarkable capacity to regenerate after injury and to adjust its size to match its host. A widely used experimental model of liver regeneration is the partial hepatectomy model in rodents in which 70% of the liver is removed. Toxin-induced models of liver regeneration have assumed growing importance, and by studying the interaction between cell damage and cell regeneration, liver regeneration have become of greater clinical relevance.
Partial hepatectomy leads to proliferation of all populations of differentiated cells within the liver, including hepatocytes, biliary epithelial cells and endothelial cells. This response is the quickest and most efficient way for liver regeneration. Cellular proliferation begins in the periportal region and proceeds toward the centers of lobules. Hepatocytes are quiescent cells under normal conditions; however, they have a practically unlimited capacity for proliferation in response to injury. Despite what appears to be a massive commitment for proliferation, the regenerating hepatocytes continue to conduct their normal metabolic duties for the host such as support of glucose metabolism.
Oval cells or intrahepatic stem cells which are located in the canals of Herring appear to form a reserve compartment capable of generating mature hepatocytes and bile duct cells after massive necrosis, toxic injury, or in any condition in which hepatocyte proliferation is impaired.
Together with hepatocytes and intrahepatic stem cells, Bone marrow stem cells could constitute a third differentiation/proliferative compartment. Bone marrow stem cells contribute to liver regeneration but with minimal capacity. BM-MSC can induce liver fibrosis via myofibroblast. Cells from amniotic fluid or umbilical cord blood can also differentiate into liver cells.
Changes in gene expression associated with regeneration are observed within minutes of hepatic resection. An array of preexisting transcription factors are rapidly activated during the priming phase of regeneration and probably participate in orchestrating the differential expression of genes in the cell cycle of the proliferating hepatocytes.
Hepatic regeneration is dividrd into three phases: priming phase, proliferation phase, and termination. The priming phase or the initiation phase is triggered by a cytokine net work. TNF-alpha and Interleukin-6 are important cytokines which initiate regeneration and stimulate quiescent hepatocytes to enter into G1 phase, and that is called priming of hepatocytes. Mitogens as EGF and HGF are important for hepatocyte proliferation phase. In addition, other contributing factors as norepnephrine, insulin, bile, and thyroxin are important for cell proliferation. Cytokines as TGF-beta1 and matrix integrin are known to inhibit proliferative responses in hepatocytes when the required mass is reached.
The hepatocyte proliferative response during liver regeneration (LR) after PH is divided into two phases: a prereplicative phase, with drastic changes in the metabolism of the remaining liver including ultrastructural, molecular structural, biochemical, and functional changes, followed by a replicative phase showing active DNA synthesis.
The process of regeneration is affected by many factors such as: nutrition, hormones, body organs, age, hyperbaric oxygenation, drugs, reactive oxygen radical scavengers, and some phytotherapeutic agents.
While major liver resections have become increasingly safe due to better understanding of anatomy and refinement of operative techniques, liver failure following partial hepatectomy still occurs from time to time and remains incompletely understood. Observationally, certain high-risk circumstances exist, namely, massive resection with small liver remnants, preexisting liver disease, and advancing age, where liver failure is more likely to happen.
The possibility of liver regeneration, together with our anatomical knowledge of the segments of the liver constitutes the basis of modern liver surgery. In transplantation medicine the demands for liver transplants can be met by the use of reduced-sized liver grafts, taken from a living donor (which is called living donor liver transplantation), this reduced graft is expected to expand by liver regeneration to a size appropriate to the body of the recipient during the postoperative course.
The concept of liver bridging has been developed for the treatment of acute liver failure, the idea being that temporary replacement of liver function by auxiliary liver grafting or hepatocyte transplantation can support life until the patient’s own liver has regenerated.
Liver transplantation is the best therapeutic option for patients with end-stage chronic liver disease or severe acute liver failure. Because of limited donor availability, attention has been focused on the possibility to restore liver mass and function through cell transplantation. Cell transplantation holds a great promise in treatment of metabolic disorders of the liver, acute liver failure, and chronic liver diseases. Cell transplantation includes either hepatocyte or stem cell transplantation. It is of less cost, minimally invasive and needs less hospitalization; this invites earlier intervention.
In conclusion, we can consider the process of liver regeneration the base of many researches and therapeutic tools of liver diseases. However, further investigations are still needed to fully understand mechanisms controlling it, how we can apply this phenomenon in the field of cell therapy, and how we can use stem cells in this field to obtain well functioning liver cells that can repopulate the liver for long time. Definite protocols for the selection of a specific cell population and for in vitro expansion/differentiation should be developed. The long-term fate of the transplanted cells should also be assessed in animal models, with respect to function, possible extra-hepatic localization and tumorigenesis.