title: Targeted migration of mesenchymal stem cells modified with CXCR4 to acute failing liver improves liver regeneration.
abstract: OBJECTIVE
  To improve the colonization rate of transplanted mesenchymal stem cells (MSCs) in the liver and effect of MSC transplantation for acute liver failure (ALF).
  
  
  METHODS
  MSC was modified with the chemokine CXC receptor 4 (CXCR4) gene (CXCR4-MSC) or not (Null-MSC) through lentiviral transduction. The characteristics of CXCR4-MSCs and Null-MSCs were determined by real-time quantitative polymerase chain reaction, Western blotting and flow cytometry. CXCR4-MSCs and Null-MSCs were infused intravenously 24 h after administration of CCl4 in nude mice. The distribution of the MSCs, survival rates, liver function, hepatocyte regeneration and growth factors of the recipient mice were analyzed.
  
  
  RESULTS
  In vitro, CXCR4-MSCs showed better migration capability toward stromal cell-derived factor-1α and a protective effect against thioacetamide in hepatocytes. In vivo imaging showed that CXCR4-MSCs migrated to the liver in larger numbers than Null-MSCs 1 and 5 d after ALF. Higher colonization led to a longer lifetime and better liver function. Either CXCR4-MSCs or Null-MSCs exhibited a paracrine effect through secreting hepatocyte growth factor and vascular endothelial growth factor. Immunohistochemical analysis of Ki-67 showed increased cell proliferation in the damaged liver of CXCR4-MSC-treated animals.
  
  
  CONCLUSIONS
  Genetically modified MSCs expressing CXCR4 showed greater colonization and conferred better functional recovery in damaged liver.
authors.affiliation: Hu-Cheng Ma, Xiao-Lei Shi, Hao-Zhen Ren, Xian-Wen Yuan, Yi-Tao Ding, Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.
authors.forename: Hu-Cheng
authors.initials: HC
authors.lastname: Ma
authors.affiliation: Hu-Cheng Ma, Xiao-Lei Shi, Hao-Zhen Ren, Xian-Wen Yuan, Yi-Tao Ding, Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.
authors.forename: Xiao-Lei
authors.initials: XL
authors.lastname: Shi
authors.affiliation: Hu-Cheng Ma, Xiao-Lei Shi, Hao-Zhen Ren, Xian-Wen Yuan, Yi-Tao Ding, Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.
authors.forename: Hao-Zhen
authors.initials: HZ
authors.lastname: Ren
authors.affiliation: Hu-Cheng Ma, Xiao-Lei Shi, Hao-Zhen Ren, Xian-Wen Yuan, Yi-Tao Ding, Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.
authors.forename: Xian-Wen
authors.initials: XW
authors.lastname: Yuan
authors.affiliation: Hu-Cheng Ma, Xiao-Lei Shi, Hao-Zhen Ren, Xian-Wen Yuan, Yi-Tao Ding, Department of Hepatobiliary Surgery, the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China.
authors.forename: Yi-Tao
authors.initials: YT
authors.lastname: Ding
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D058948:Cell Tracking / Q000379:methods; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D017114:Liver Failure, Acute / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008115:Liver Regeneration; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008819:Mice, Nude; D019899:Paracrine Communication; D019718:Receptors, CXCR4 / Q000096:biosynthesis* / Q000235:genetics; D013853:Thioacetamide; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C527276:CXCR4 protein, human; C066855:HGF protein, human; D019718:Receptors, CXCR4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C485184:enhanced green fluorescent protein; D013853:Thioacetamide; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor
keywords: Acute liver failure; Cell mobilization; Cell transplantation; Chemokine CXC receptor 4; Mesenchymal stem cells