La transplantation d’hépatocytes chez le rat Long Evans Cinnamon, modèle animal de la maladie de Wilson
Wilson’s disease (WD) is a hereditary metabolic disease caused by a deficiency of copper-transporting ATP7B, resulting in copper accumulating to toxic levels in the liver.  Its manifestations range from acute or chronic hepatic insufficiency to fulminant liver failure. The mainstay of therapy is the use of chelating agents.  However selected patients may also require orthotopic liver transplantation (OTL), an invasive and complex procedure with life-long implications.  Hepatocyte transplantation  is an appealing alternative to OLT.  Its safety and efficacy  were evaluated in the animal model of WD, the Long Evans Cinnamon (LEC) rat.  Twelve LEC rats received an intrasplenic injection of 2,6 x 105 – 3,6 x 107 hepatocytes obtained from LE donor rats.  They were followed for 6 months before sacrifice.  They were then compared to a control group of twelve rats.  No difference was found when comparing their weights, biochemical parameters such as liver function tests and bilirubin, as well as their biliary and hepatic copper concentrations.  However, the ceruloplasmin oxydase activity was improved in the transplanted rats (49,6 ± 31,5 versus 8,9 ± 11,7).  After sacrifice, histologic evaluation and demonstration of atp7b mRNA in the recipient liver were performed.  There was evidence of histological improvement and atp7b mRNA was found in 58% of transplanted rats with an expression of 11,9% ± 13,6 when compared to a normal LE rat.  Evidence of successful engraftment of the transplanted cells was found in every transplanted rat using the technique of immunohistochemistry.  These encouraging results are in accordance with previous studies on hepatocyte transplantation in the LEC rat.  Its application to the human clinical setting is the next step, as it has already been tried in other metabolic liver diseases.
Wilson ATP7B Hepatocyte transplantation LEC rat Metabolic disease