title: Mesenchymal Stromal Cell-Derived Factors Promote Tissue Repair in a Small-for-Size Ischemic Liver Model but Do Not Protect against Early Effects of Ischemia and Reperfusion Injury.
abstract: Loss of liver mass and ischemia/reperfusion injury (IRI) are major contributors to postresectional liver failure and small-for-size syndrome. Mesenchymal stromal cell- (MSC-) secreted factors are described to stimulate regeneration after partial hepatectomy. This study investigates if liver-derived MSC-secreted factors also promote liver regeneration after resection in the presence of IRI. C57BL/6 mice underwent IRI of 70% of their liver mass, alone or combined with 50% partial hepatectomy (PH). Mice were treated with MSC-conditioned medium (MSC-CM) or unconditioned medium (UM) and sacrificed after 6 or 24 hours (IRI group) or after 48 hours (IRI + PH group). Blood and liver tissue were analyzed for tissue injury, hepatocyte proliferation, and gene expression. In the IRI alone model, serum ALT and AST levels, hepatic tissue damage, and inflammatory cytokine gene expression showed no significant differences between both treatment groups. In the IRI + PH model, significant reduction in hepatic tissue damage as well as a significant increase in hepatocyte proliferation was observed after MSC-CM treatment.
  
  
  CONCLUSIONS
  Mesenchymal stromal cell-derived factors promote tissue regeneration of small-for-size livers exposed to ischemic conditions but do not protect against early ischemia and reperfusion injury itself. MSC-derived factors therefore represent a promising treatment strategy for small-for-size syndrome and postresectional liver failure.
authors.affiliation: Department of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, Netherlands ; Department of Surgery, Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Suomi M G
authors.initials: SM
authors.lastname: Fouraschen
authors.affiliation: Department of Surgery, Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Joshua H
authors.initials: JH
authors.lastname: Wolf
authors.affiliation: Department of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, Netherlands.
authors.forename: Luc J W
authors.initials: LJ
authors.lastname: van der Laan
authors.affiliation: Department of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, Netherlands.
authors.forename: Petra E
authors.initials: PE
authors.lastname: de Ruiter
authors.affiliation: Department of Transplant Immunology, Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4318, USA.
authors.forename: Wayne W
authors.initials: WW
authors.lastname: Hancock
authors.affiliation: Department of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, Netherlands.
authors.forename: Job P
authors.initials: JP
authors.lastname: van Kooten
authors.affiliation: Department of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, Netherlands.
authors.forename: Monique M A
authors.initials: MM
authors.lastname: Verstegen
authors.affiliation: Department of Surgery, Penn Transplant Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kim M
authors.initials: KM
authors.lastname: Olthoff
authors.affiliation: Department of Surgery, Erasmus MC-University Medical Center, 3015 CE Rotterdam, Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: de Jonge
mesh_terms: D000818:Animals; D001835:Body Weight; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007511:Ischemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008111:Liver Function Tests; D008115:Liver Regeneration; D008297:Male; D013058:Mass Spectrometry; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D009929:Organ Size; D015427:Reperfusion Injury / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D017077:Culture Media, Conditioned