Cell therapy for Crigler-Najjar type I syndrome using human adult liver stem cells

Crigler-Najjar Syndrome type I (CNSI) is a recessive disorder affecting bilirubin metabolism. Bilirubin-induced neurological damage leads to early lethality unless phototherapy is applied from birth. Treatment becomes less effective with growth and liver transplantation is then required. Therefore, alternative treatment strategies for this disease are necessary. Stem cells are very important in that they can be differentiated into specialized cell types, like hepatocytes, and used as a platform for gene delivery to correct single gene defects. The goal of this project is to evaluate the use of human adult liver stem cells (HLSC) in treating CNSI in a mouse model represented by Ugt1 deficient mice closely mimicking the pathological manifestations in CNSI patients. We have demonstrated that HLSC cells can be differentiated into functional hepatocytes in vitro and these hepatocytes contributed to regeneration of the liver parenchyma in vivo. We propose to develop therapeutic approaches based on cell therapy with HLSCs transplanted into Ugt1 deficient mice in order to obtain a permanent expression of the wild type gene in mutant livers with the final goal of achieving organ repopulation and long-term recovery of liver functions. The results obtained will set the premises for use of HLSC for cell therapy of CNSI and other genetic metabolic diseases of the liver.