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.
Pubmed ID: 26304833 RIS Download
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Biomedical technology research center and training resource for the study of the structure of partially ordered biological molecules, complexes of biomolecules and cellular structures under conditions similar to those present in living cells and tissues. The goal of research at BioCAT is to determine the detailed structure and mechanism of action of biological systems at the molecular level. The techniques used are X-ray fiber diffraction, X-ray solution scattering and X-ray micro-emission and micro-absorption spectroscopy, with an emphasis on time-resolved studies and the development of novel techniques.
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