AbstractsBiology & Animal Science

Adult derived human liver stem/progenitor cells for the treatment of Crigler Najjar syndrome type 1 : a functionality study of long-term transplantation in the Gunn rat

by Cedric Maerckx




Institution: Université Catholique de Louvain
Department: Pôle de Pédiatrie
Year: 2014
Keywords: Stem cell therapy; Hepatology; Crigler-Najjar; Gunn rat
Record ID: 1077266
Full text PDF: http://hdl.handle.net/2078.1/141749


Abstract

In the last decade, stem cell therapy has raised much hope to treat patients presenting a variety of illnesses. Liver progenitor cells offer a promising alternative for the treatment of hepatic diseases. Despite the enthusiasm, cell efficiency need to be assessed on the route to clinic. This study is part of a larger medical translational research project that aims to treat inherited metabolic liver diseases with stem cell therapy. In the present study we evaluate the presence of progenitor cells in healthy adult rat liver which would display the same advanced hepatogenic profile as that decribed in human adult liver derived progenitor cells (ADHLSC). We observed that rat progenitor cells homologous to ADHLSC cannot be easily obtained even when the same isolation and culture protocol was applied. However, we isolated a novel type of rat liver progenitor cell population: fibroblastic-like liver derived cells (rFLDC) which expressed hepatic and biliary markers. Then we focused on the ability of transplanted ADHLSC to correct a UGT1A1 activity deficiency in the Gunn rat model homologous to the human hyperbilirubinemic Crigler-Najjar syndrome type I. We demonstrated that ADHLSCs were able to integrate into the Gunn rat liver parenchyma and these rats exhibit a metabolic effect 3 months post-transplantation and maintained over a 6 months period. Finally, using 111Indium-oxine labeled ADHLSC, we demonstrate the engraftment and the homing of cells preferentially within the liver parenchyma. All together, these results make ADHLSC an attractive candidate for cell therapy treatment of Crigler-Najjar type I syndrome. (MED - Sciences médicales)  – UCL, 2014