title: A fat option for the pig: hepatocytic differentiated mesenchymal stem cells for translational research.
abstract: BACKGROUND
  Extended liver resection is the only curative treatment option of liver cancer. Yet, the residual liver may not accomplish the high metabolic and regenerative capacity needed, which frequently leads to acute liver failure. Because of their anti-inflammatory and -apoptotic as well as pro-proliferative features, mesenchymal stem cells differentiated into hepatocyte-like cells might provide functional and regenerative compensation. Clinical translation of basic research requires pre-clinical approval in large animals. Therefore, we characterized porcine mesenchymal stem cells (MSC) from adipose tissue and bone marrow and their hepatocyte differentiation potential for future assessment of functional liver support after surgical intervention in the pig model.
  
  
  METHODS
  Mesenchymal surface antigens and multi-lineage differentiation potential of porcine MSC isolated by collagenase digestion either from bone marrow or adipose tissue (subcutaneous/visceral) were assessed by flow cytometry. Morphology and functional properties (urea-, glycogen synthesis and cytochrome P450 activity) were determined during culture under differentiation conditions and compared with primary porcine hepatocytes.
  
  
  RESULTS
  MSC from porcine adipose tissue and from bone marrow express the typical mesenchymal markers CD44, CD29, CD90 and CD105 but not haematopoietic markers. MSC from both sources displayed differentiation into the osteogenic as well as adipogenic lineage. After hepatocyte differentiation, expression of CD105 decreased significantly and cells adopted the typical polygonal morphology of hepatocytes. Glycogen storage was comparable in adipose tissue- and bone marrow-derived cells. Urea synthesis was about 35% lower in visceral than in subcutaneous adipose tissue-derived MSC. Cytochrome P450 activity increased significantly during differentiation and was twice as high in hepatocyte-like cells generated from bone marrow as from adipose tissue.
  
  
  CONCLUSIONS
  The hepatocyte differentiation of porcine adipose tissue-derived MSC was shown for the first time yielding hepatocyte-like cells with specific functions similar in bone marrow and subcutaneous adipose tissue-derived MSC. That makes them good pre-clinical candidates for supportive approaches after liver resection in the pig.
authors.affiliation: University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103, Germany. Electronic address: sandra.brueckner@medizin.uni-leipzig.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Brückner
authors.affiliation: University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103, Germany; TRM, Translational Centre for Regenerative Medicine, Philipp-Rosenthal-Str. 55, Leipzig D-04103, Germany. Electronic address: hans-michael.tautenhahn@medizin.uni-leipzig.de.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Tautenhahn
authors.affiliation: University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103, Germany. Electronic address: sandra.pelz@medizin.uni-leipzig.de.
authors.forename: Sandra
authors.initials: S
authors.lastname: Winkler
authors.affiliation: University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103, Germany. Electronic address: peggy.stock@medizin.uni-leipzig.de.
authors.forename: Peggy
authors.initials: P
authors.lastname: Stock
authors.affiliation: University Hospital Ulm, First Department of Medicine, Albert-Einstein-Allee 23, Ulm D-89081, Germany. Electronic address: matthias.dollinger@uniklinik-ulm.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Dollinger
authors.affiliation: University Hospital Leipzig, Department of Visceral, Transplantation, Thoracic and Vascular Surgery, Liebigstraße 21, Leipzig D-04103, Germany; TRM, Translational Centre for Regenerative Medicine, Philipp-Rosenthal-Str. 55, Leipzig D-04103, Germany. Electronic address: bruno.christ@medizin.uni-leipzig.de.
authors.forename: Bruno
authors.initials: B
authors.lastname: Christ
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation; D002478:Cells, Cultured; D005260:Female; D022781:Hepatocytes / Q000502:physiology*; D050152:Intra-Abdominal Fat / Q000166:cytology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D010641:Phenotype; D050151:Subcutaneous Fat / Q000166:cytology; D013552:Swine; D057170:Translational Research, Biomedical / Q000379:methods
keywords: Adipose tissue; Bone marrow; Hepatocyte; Mesenchymal stem cells; Pig; Stem cell differentiation; Stem cell therapy