title: Bile acids induce hepatic differentiation of mesenchymal stem cells.
abstract: Mesenchymal stem cells (MSC) have the potential to differentiate into multiple cell lineages and their therapeutic potential has become obvious. In the liver, MSC are represented by stellate cells which have the potential to differentiate into hepatocytes after stimulation with growth factors. Since bile acids can promote liver regeneration, their influence on liver-resident and bone marrow-derived MSC was investigated. Physiological concentrations of bile acids such as tauroursodeoxycholic acid were able to initiate hepatic differentiation of MSC via the farnesoid X receptor and transmembrane G-protein-coupled bile acid receptor 5 as investigated with knockout mice. Notch, hedgehog, transforming growth factor-β/bone morphogenic protein family and non-canonical Wnt signalling were also essential for bile acid-mediated differentiation, whereas β-catenin-dependent Wnt signalling was able to attenuate this process. Our findings reveal bile acid-mediated signalling as an alternative way to induce hepatic differentiaion of stem cells and highlight bile acids as important signalling molecules during liver regeneration.
authors: Clinic of Gastroenterology, Hepatology and Infectious Diseases.
authors: Iris
authors: I
authors: Sawitza
authors: Clinic of Gastroenterology, Hepatology and Infectious Diseases.
authors: Claus
authors: C
authors: Kordes
authors: Clinic of Gastroenterology, Hepatology and Infectious Diseases.
authors: Silke
authors: S
authors: Götze
authors: Department of General Pediatrics, Neonatology and Pediatric Cardiology, Heinrich Heine University, Moorenstraße 5, 40225 Düsseldorf, Germany.
authors: Diran
authors: D
authors: Herebian
authors: Clinic of Gastroenterology, Hepatology and Infectious Diseases.
authors: Dieter
authors: D
authors: Häussinger
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D055166:Hepatic Stellate Cells / Q000166:cytology* / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001647:Bile Acids and Salts