title: Mesenchymal stem cell-conditioned medium reduces liver injury and enhances regeneration in reduced-size rat liver transplantation.
abstract: BACKGROUND
  Mesenchymal stem cell (MSC) therapy can prevent parenchymal cell loss and promotes tissue repair through the action of trophic, secreted molecules. In this study, we investigated whether MSC-conditioned medium (MSC-CM) could protect hepatocytes and sinusoidal endothelial cells (SECs) and stimulate their regeneration in 50% reduced-size liver transplantation (RSLT).
  
  
  METHODS
  Rats were randomly divided into three groups: sham-operated group, MSC-CM group (rats with 50% RSLT receiving MSC-CM infusion), and medium group (rats with 50% RSLT receiving medium therapy). Graft function, proinflammatory cytokines, incidence of apoptosis, proliferation of hepatocytes and SECs, and the expression of vascular endothelial growth factor and matrix metallopeptidase 9 were assessed in this study.
  
  
  RESULTS
  Systemic infusion of MSC-CM prevented the release of liver injury biomarkers and provided a significant survival benefit. Furthermore, MSC-CM therapy resulted in reduction of apoptosis of hepatocytes and SECs. The number of proliferating hepatocytes and SECs increased 1.2- and 1.6-fold, respectively, accompanied by a decrease in the expression levels of several proinflammatory cytokines and a noticeable decrease in infiltration of neutrophils and activation of Kupffer cells. Also, increased expression of vascular endothelial growth factor and matrix metallopeptidase 9 in the grafts was observed after MSC-CM therapy.
  
  
  CONCLUSIONS
  These data suggest that MSC-CM therapy in RSLT provides trophic support to the injured liver by inhibiting SEC and hepatocellular death and stimulating their regeneration.
authors.affiliation: Department of General Surgery, Xinhua Hospital, Shanghai Jiaotong University Medical School, Shanghai, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Du
authors.forename: Cuifeng
authors.initials: C
authors.lastname: Wei
authors.forename: Kun
authors.initials: K
authors.lastname: Cheng
authors.forename: Baosan
authors.initials: B
authors.lastname: Han
authors.forename: Jiqi
authors.initials: J
authors.lastname: Yan
authors.forename: Mingjun
authors.initials: M
authors.lastname: Zhang
authors.forename: Chenghong
authors.initials: C
authors.lastname: Peng
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000293:injuries* / Q000378:metabolism / Q000473:pathology*; D008115:Liver Regeneration / Q000187:drug effects* / Q000502:physiology; D016031:Liver Transplantation / Q000473:pathology*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9
keywords: Ischemia-reperfusion injury; Liver regeneration; Mesenchymal stem cells; Reduced-size liver transplantation; Sinusoidal endothelial cells