The major impediment to realizing the therapeutic potential of hepatocyte transplantation has been the limited availability of human hepatocytes and the number of liver cells that can be transplanted safely at one time. The maximum number of hepatocytes that has been transplanted safely without causing adverse effects, such as portal hypertension, is the equivalent of about 5% of total liver cell mass. Clinical trials, in which 7.5 billion normal allogeneic hepatocytes (representing -5% of the hepatocyte mass) were transplanted into a 10-year-old girl with Crigler-Najjar syndrome type 1, has demonstrated the long-term safety of hepatocyte transplantation1. However, in such studies the correction of metabolic disorder was not complete as very little proliferation of the donor hepatocytes in the host liver was observed. Thus it appears that greater than 5% replacement of the hepatocellular mass is required for near-complete correction of many metabolic liver diseases. There is an urgent need to develop preparative regimens of hepatocyte transplantation that would provide a selective growth advantage to the transplanted normal hepatocytes over the host hepatocytes, so that the engrafted cells could progressively replace the diseased host liver cells.
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