الفهرس 
Historical Review of Hepatocyte TransplantationOnly 14 pages are availabe for public view
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Abstract
Many of the major advances in clinical medicine over the past 25 years have been in the field of transplantation. The tremendous growth in this field would not have been possible without basic research to elucidate the mechanism of alloreactivity permitting development of focused strategies to control the rejection response. Organ transplantation is now an established therapeutic modality which enables a damaged organ to be replaced with a functioning new one. Since the 1960s the fundamentals of transplantation immunology have been better understood from the results of animal experimentation. Immunosuppressive drugs are now available to control graft rejection and while successful human to human transplants were making headlines there is dearth of donor organs for transplantation. This has lead to the emergence of xenotransplantation as an alternative to allogenic transplantation.
The liver plays a vital role in the biochemical metabolism of the body and has very complicated functions, such as the production of glucose proteins and lipids the metabolism of vitamines and hormones, and the secretion and excretion of bile and other waste products. Fulminant hepatic failure (FHF) is a multifactorial process leading to instability and derangement of essential functions such as acid-base balance, energy supply and thermoregulation. If not rapidly reversed, complications will lead to hepatic coma by affecting the brain and kidneys. With additional organ failure recovery becomes irreversible and leads to a high patient mortality. The catastrophic failure of a previous normal liver is one of the most challenging emegencies in clinical medicine.
Orthotopic liver transplantation (OLT)has been used for the treatment of various liver diseases, especially FHF. Within the last few years liver transplantation has evolved as the treatment of choice for patients with end stage liver diseases. However it is a major surgical procedure that requires life-long immunosuppressive drugs.
The occasional spontaneous recovery of patients with FHF suggests that if temporary metabolic support could be provided during the period of maximum hepatic insufficiency, the damaged liver could regenerate and the clinical outcome might be improved.
Hepatic support modalities functionally remove the accumulated toxic substances from the plasma of patients with acute liver failure. The procedures available for clinical evaluation are exchange transfusion charcoal hemoperfusion cross circulation cross perfusion dialysis and extracorporeal whole liver and liver cell perfusion. These procedures are no longer used as they are ineffective in the management of FHF.
Studies indicate that the major problem in FHF is the loss of hepatocytes rather than a deficiency in the proliferation of surviving hepatocytes. Therefore salvaging the injured liver in fulminant hepatic failure may require liver repopulation. Hence hepatocyte transplantation offers the plausible potential in FHF.
The mortality of hepatic failure induced experimwarm heat iskaemia was substantially reduced by hepatocyte transplantation. For example pharmacological doses of D-galactosamine or dimethylnitrosamine cause hepatic necrosis resulting in a mortality over 90%.In contrast .after hepatocyte transplantation in various ways. the rate of mortality induced by these agents is significantly reduced with 60% survival of the recipients.
Hepatocyte transplantation provides improvement in liver function and restores homeostasis. The beneficial effects can be anticipated if liver function is normalized the typical complications of liver failure will be alleviated dependent organs will continue to function normally ,and metabolic stability will promote rapid liver regeneration. These factors will also contribute to a shorter clinical course and lower cost. Hepatocyte transplantation represents monocomponent therapy and has a number of potential advantages in contrast to OLT. Firstly hepatocyte transplantation is accomplished by the injection of isolated cells and no vascular anastomosis is required. Secondly donor hepatocytes can be easily obtained from resected segments. Thirdly, autotransplantation of hepatocytes is another option for hepatocyte transplantation.
Hepatocyte transplantation appears to have an immense therapeutic potential to overcome the debilitating effects of FHF. It thus offers a promising alternative to the OLT, to overcome acute immune rejection .This is accomplished in accordance with the efficacy and compatibility of the transplanted hepatocytes which replenish the loss of hepatocytes evident in FHF. With the advent of novel transplantation systems strategies are now being focused to reconstitute host liver hepatocytes in the recipient so as to sustain the metabolic and biochemical functions for a greater period of time