Abstract
Orthotopic liver transplantation continues to be the only effective therapy for patients with end-stage liver disease. Unfortunately, many of these patients are not considered transplant candidates, lacking effective therapeutic options that would address both the irreversible progression of their hepatic failure and the control of their portal hypertension. In this prospective study, a swine model was exploited to induce subacute liver failure. Autologous hepatocytes, isolated from the left hepatic lobe, were transplanted into the mesenteric lymph nodes (LNs) by direct cell injection. At 30-60 days after transplantation, hepatocyte engraftment in LNs was successfully identified in all transplanted animals with the degree of ectopic liver mass detected being proportional to the induced native liver injury. These ectopic livers developed within the LNs showed remarkable histologic features of swine hepatic lobules, including the formation of sinusoids and bile ducts. On the basis of our previous tyrosinemic mouse model and the present pig models of induced subacute liver failure, the generation of auxiliary liver tissue using the LNs as hepatocyte engraftment sites represents a potential therapeutic approach to supplement declining hepatic function in the treatment of liver disease.