Adult Stem Therapy for Patients With Liver Insufficiency

The liver in an adult healthy body maintains a balance between cell gain and cell loss. Though normally proliferatively quiescent, hepatocyte loss such as that caused by partial hepatectomy, uncomplicated by virus infection or inflammation, invokes a rapid regenerative response to restore liver mass. This restoration of moderate cell loss and 'wear and tear' renewal is largely achieved by hepatocyte self-replication. More severe liver injury can activate a potential stem cell compartment located within the intrahepatic biliary tree, giving rise to cords of bipotential, so-called, oval cells within the lobules that can differentiate into hepatocytes and biliary epithelial cells. A third population of stem cells with hepatic potential reside in the bone marrow; these haematopoietic stem cells can contribute to the albeit low renewal rate of hepatocytes, make a more significant contribution to regeneration and even completely restore normal function in a murine model of hereditary tyrosinaemia.

A recent abstract has suggested that an astonishingly high number of bone marrow cells (~25% of liver parenchyma occupied by bone marrow-derived cells) will engraft and differentiate into hepatocytes in a model of cirrhosis in the mouse when injected intravenously. More importantly, this bone marrow infusion resulted in significant improvements in liver function (serum albumin) within the cirrhotic animals.

This is a safety and toxicity study in five patients with chronic liver disease. Each will receive autologous stem cells 10 to the sixth cells via the hepatic artery or portal vein under image guided scanning. Patients will be followed for a total of 60 days.