TREATMENT OF LIVER-BASED GENETIC METABOLIC DISORDERS WITH BONE MARROW-DERIVED HEPATIC STEM CELLS

Stem cells are young cells having the ability to proliferate giving rise to specialized cells in many organs and tissues. Stem cell transplantation could be used as an alternative to whole liver transplantation for the treatment of many genetic disorders of liver metabolism, thus obviating the problem of donors’ shortage and eliminating the need for major surgery. It has already been shown that many liver-based inherited metabolic disorders can be treated by selective replacements of liver cells, but the supply of mature liver cells is subjected to the same limitations as the whole organ. Working in collaboration with the Cedars-Sinai Medical Center of Los Angeles, we recently participated in a project that resulted in repopulation of a diseased rat liver with stem cells isolated from the bone marrow of a healthy animal. After transplantation, these stem cells differentiated into liver cells reducing the extent of liver damage in the recipient animal. Such stem cells could also be isolated from human bone marrow, and could thus be obtained from millions of potential living donors with simple procedures. The aim of the present project is to transplant hepatic stem cells from the bone marrow of a normal rat into the liver of a rat with congenital deficiency of bilirubin conjugation, similar to Crigler-Najjar disease in humans, in order to verify if these cells can cure a hepatic metabolic disorder.