**4. Hepatocyte and stem cells transplantation**

Additional approaches, as therapeutic alternative in attempt to reduce the significant mortality in the waiting list for liver transplantation is hepatocyte transplantation. A number of experiments have shown the feasibility of total liver parenchymal cell replacement by transplanted hepatocytes.[128-132] Hepatocyte transplantation might be able to bridge a period needed for regeneration of the acute liver failure patient's own liver or stretch the waiting time for a suitable liver donation. Although the first animal experiments with this technique began in 1967 [133], it was first applied in humans only in 1992.[134] Isolated Hepatocyte transplantation has long been recognized as a potential treatment for life-threatening liver disease. The basis for proceeding with clinical trials has been provided by extensive laboratory work in animal models.[135-140] The most important advantage of this treatment compared to liver transplantation, is its simplicity, since no surgery is required for cell implantation. The cell transplantation has been used for, temporary metabolic support of patients in end-stage liver failure awaiting whole-organ transplantation, as method to support liver function and facilitate the regeneration of the native liver in cases of fulminant hepatic failure, and in a manner similar to gene therapy as a form of "cellular therapy" for patients with genetic defects in vital liver functions. The patients can be treated by the infusion of 107-1010 allogenic hepatocytes, obtained from adult cadaveric livers, into the splenic artery or portal vein.[141] The main obstacle to wider usage of hepatocyte transplantation is the rapid elimination of the transplanted hepatocytes by recipient macrophages.[142]

Alternatives to the transplantation of allogenic human hepatocytes include the transplantation of hepatocytes derived from fetal, adult, or embryonic stem cells, engineered immortalized cells, or hepatocytes derived from other animal species.[143] Stem cells are one of the best approaches to obtaining cell stores. This approach can be used for clinical treatment by selecting small cell population that could effectively repopulate the host liver.[144]
