Intrahepatic transplantation of normal hepatocytes prevents Wilson's disease in Long-Evans cinnamon rats

Liver NK cells expressing TRAIL are toxic against self hepatocytes in mice

“…Previous studies have demonstrated therapeutic efficacy of hepatocyte transplantation through a variety of liver disease models. 46,47 Particularly for the treatment of inherited metabolic disease, a technique for transplantation of genetically modified autologous hepatocytes, which have the advantage of no T cell-mediated rejection, is being developed. Although the host liver represents an ideal site for transplanted hepatocytes in terms of the unique hepatic organization and interactions with nonparenchymal liver cells, 48 insufficient intrahepatic engraftment of transplanted hepatocytes, even those that are autologous, remains a major obstacle.…”

Feasibility of Hepatocyte Transplantation-Based Therapies for Primary Hyperoxalurias

“…In each of these instances, recipient hepatocytes undergo spontaneous necrosis or apoptosis, providing stimuli for compensatory hyperplasia to transplanted hepatocytes, leading to progressive replacement of the host hepatocytes. To a lesser extent, repopulation of the host liver by transplanted hepatocytes is seen in mutant Long-Evans Cinnamon rats with hepatocellular copper overload (a model of human Wilson’s disease) [21]. …”

Liver gene therapy: advances and hurdles

“…This higher efficacy probably reflects the favorable environment in regenerating livers (vascular remodelling, secretion of growth factors and cytokines, such as hepatocyte growth factor and VEGF). 3,8,41,83,84 Transplanted hepatocytes did not significantly proliferate in the regenerating livers, presumably because host hepatocytes started to proliferate within a few hours post-partial-hepatectomy, with DNA synthesis peaking 24 h postsurgery, and had restored the initial total hepatocyte mass within 4 days in rats. 8 Accordingly, when host hepatocytes were prevented from proliferating, small clusters of proliferating donor hepatocytes could be detected by day 4 posthepatectomy.…”

“…Interestingly, spontaneous extensive liver repopulation with healthy hepatocytes occurred in some inherited liver diseases when the genetic mutation caused the death of diseased hepatocytes, as in Alb-uPA transgenic mice. [1][2][3]67,88 To apply this principle to most liver disorders, in which host diseased hepatocytes could compete with donor hepatocytes for liver repopulation, animals were pretreated with retrorsine or subjected to whole liver irradiation to inhibit proliferation ability of host hepatocytes before cell transplantation. 85,89,90 In combination with a strong regenerative pressure (eg twothirds partial hepatectomy, thyroid hormone administration, ischemia-reperfusion injury or FasL gene transfer), a nearly complete repopulation of host liver by donor hepatocytes was obtained after transplantation of 0.5% of the recipient liver mass.…”

“…Accumulation of toxic products in hepatocytes leads to extensive hepatoxicity, and in such situations, healthy or corrected hepatocytes have a selective growth advantage over resident diseased hepatocytes. [1][2][3] The latter category includes metabolic deficiencies, such as Crigler-Najjar syndrome type I, ornithine transcarbamylase (OTC) deficiency, type IIa familial hypercholesterolemia and coagulation defects such as hemophilia A and B and afibrogenemia. Acquired hepatic diseases could also benefit from genetic approaches, such as viral hepatitis if hepatocytes could be made refractory to the replication of hepatitis B or C viruses, liver cancers if transgenes could trigger cell suicide, and fulminant liver failure if liver could be protected from massive injury.…”