title: Attenuation of Postoperative Acute Liver Failure by Mesenchymal Stem Cell Treatment Due to Metabolic Implications.
abstract: OBJECTIVE
  To prevent posthepatectomy acute liver failure after extended resection by treatment with mesenchymal stem cells (MSCs).
  
  
  BACKGROUND
  Liver tumors often require extended liver resection, overburdening metabolic and regenerative capacities of the remnant organ. Resulting dysfunction and failure may be improved by the proregenerative characteristics of MSCs.
  
  
  METHODS
  Extended liver resection was performed in (DPPIV)-deficient F344-Fischer rats. Wild-type animals served as donors of peritoneal adipose-derived MSCs. These were predifferentiated in vitro into hepatocytic cells and delivered to the liver by splenic application. Liver-related blood parameters (international normalized ratio, bilirubin, aspartate aminotransferase, alanine aminotransferase) and liver histology (hematoxylin-eosin, Sudan III) were determined to monitor liver function. Metabolic changes were assessed by metabolomic analyses in the remnant liver and the serum. Liver damage and regeneration were quantified by determination of the apoptotic and proliferation rates.
  
  
  RESULTS
  MSCs supported survival after partial hepatectomy. They decreased liver-related blood parameters indicative for the improvement of liver function. The extensive lipid accumulation in hepatocytes illustrating the metabolic overload after resection was attenuated. Treatment with MSCs normalized imbalance of amino acids, acylcarnitines, sphingolipids, and glycerophospholipids in the liver and blood. Furthermore, MSCs decreased the apoptotic rate and increased the proliferation rate. The experimental time period (48 hours) was too short to allow for integration of MSCs into the host liver. Thus, the mode of action was probably indirect.
  
  
  CONCLUSIONS
  MSCs ameliorated hepatic dysfunction and improved liver regeneration after extended resection by paracrine mechanisms. They may represent a new therapeutic option to treat posthepatectomy acute liver failure.
authors.affiliation: *Department of Visceral, Transplantation, Thoracic and Vascular Surgery, University Hospital Leipzig AöR, Leipzig, Germany †Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany ‡Department of Metabolomics, Helmholtz Centre for Environmental Research GmbH-UFZ, Leipzig, Germany §Institute of Pharmacy, Faculty of Biosciences, Pharmacy and Psychology, University of Leipzig, Leipzig, Germany ¶Department of Proteomics, Helmholtz Centre for Environmental Research GmbH-UFZ, Leipzig, Germany ||Department of Biotechnology, Chemistry and Environmental Engineering, Aalborg University, Aalborg, Denmark.
authors.forename: Hans-Michael
authors.initials: HM
authors.lastname: Tautenhahn
authors.forename: Sandra
authors.initials: S
authors.lastname: Brückner
authors.forename: Sven
authors.initials: S
authors.lastname: Baumann
authors.forename: Sandra
authors.initials: S
authors.lastname: Winkler
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Otto
authors.forename: Martin
authors.initials: M
authors.lastname: von Bergen
authors.forename: Michael
authors.initials: M
authors.lastname: Bartels
authors.forename: Bruno
authors.initials: B
authors.lastname: Christ
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D006498:Hepatectomy; D007124:Immunoenzyme Techniques; D020287:In Situ Nick-End Labeling; D017114:Liver Failure, Acute / Q000378:metabolism* / Q000628:therapy*; D008111:Liver Function Tests; D008115:Liver Regeneration / Q000502:physiology; D045164:Mesenchymal Stem Cell Transplantation; D055432:Metabolomics; D051381:Rats; D011916:Rats, Inbred F344; D013194:Staining and Labeling