title: Identification of Pathways in Liver Repair Potentially Targeted by Secretory Proteins from Human Mesenchymal Stem Cells.
abstract: BACKGROUND
  The beneficial impact of mesenchymal stem cells (MSC) on both acute and chronic liver diseases has been confirmed, although the molecular mechanisms behind it remain elusive. We aim to identify factors secreted by undifferentiated and hepatocytic differentiated MSC in vitro in order to delineate liver repair pathways potentially targeted by MSC.
  
  
  METHODS
  Secreted factors were determined by protein arrays and related pathways identified by biomathematical analyses.
  
  
  RESULTS
  MSC from adipose tissue and bone marrow expressed a similar pattern of surface markers. After hepatocytic differentiation, CD54 (intercellular adhesion molecule 1, ICAM-1) increased and CD166 (activated leukocyte cell adhesion molecule, ALCAM) decreased. MSC secreted different factors before and after differentiation. These comprised cytokines involved in innate immunity and growth factors regulating liver regeneration. Pathway analysis revealed cytokine-cytokine receptor interactions, chemokine signalling pathways, the complement and coagulation cascades as well as the Januskinase-signal transducers and activators of transcription (JAK-STAT) and nucleotide-binding oligomerization domain-like receptor (NOD-like receptor) signalling pathways as relevant networks. Relationships to transforming growth factor β (TGF-β) and hypoxia-inducible factor 1-α (HIF1-α) signalling seemed also relevant.
  
  
  CONCLUSIONS
  MSC secreted proteins, which differed depending on cell source and degree of differentiation. The factors might address inflammatory and growth factor pathways as well as chemo-attraction and innate immunity. Since these are prone to dysregulation in most liver diseases, MSC release hepatotropic factors, potentially supporting liver regeneration.
authors.affiliation: Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital of Leipzig, Liebigstraße 21, 04103 Leipzig, Germany. sandra.pelz@medizin.uni-leipzig.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Winkler
authors.affiliation: Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital of Leipzig, Liebigstraße 21, 04103 Leipzig, Germany. madlen.hempel@medizin.uni-leipzig.de.
authors.forename: Madlen
authors.initials: M
authors.lastname: Hempel
authors.affiliation: Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital of Leipzig, Liebigstraße 21, 04103 Leipzig, Germany. sandra.brueckner@medizin.uni-leipzig.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Brückner
authors.affiliation: Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital of Leipzig, Liebigstraße 21, 04103 Leipzig, Germany. hans-michael.tautenhahn@medizin.uni-leipzig.de.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Tautenhahn
authors.affiliation: Department of General, Visceral and Vascular Surgery, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany. roland.kaufmann@med.uni-jena.de.
authors.forename: Roland
authors.initials: R
authors.lastname: Kaufmann
authors.affiliation: Applied Molecular Hepatology Laboratory, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital of Leipzig, Liebigstraße 21, 04103 Leipzig, Germany. bruno.christ@medizin.uni-leipzig.de.
authors.forename: Bruno
authors.initials: B
authors.lastname: Christ
mesh_terms: D020410:Activated-Leukocyte Cell Adhesion Molecule / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008115:Liver Regeneration / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D000070576:NLR Proteins / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D020410:Activated-Leukocyte Cell Adhesion Molecule; D018925:Chemokines; D016207:Cytokines; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000070576:NLR Proteins; D016212:Transforming Growth Factor beta; D018799:Intercellular Adhesion Molecule-1
keywords: adipose tissue; bone marrow; chemokines; cytokines; hepatocytic differentiation; liver regeneration; mesenchymal stem cells; secretome