Hu-Cheng Ma1, Xiao-Lei Shi1, Hao-Zhen Ren1, Xian-Wen Yuan1, Yi-Tao Ding1. 1. 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.
Abstract
AIM: 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. CONCLUSION: Genetically modified MSCs expressing CXCR4 showed greater colonization and conferred better functional recovery in damaged liver.
AIM: 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. CONCLUSION: Genetically modified MSCs expressing CXCR4 showed greater colonization and conferred better functional recovery in damaged liver.
Authors: Yao Liang Tang; Wuqiang Zhu; Min Cheng; Lijuan Chen; John Zhang; Tao Sun; Raj Kishore; M Ian Phillips; Douglas W Losordo; Gangjian Qin Journal: Circ Res Date: 2009-04-30 Impact factor: 17.367
Authors: Myrtle Y Gordon; Natasa Levicar; Madhava Pai; Philippe Bachellier; Ioannis Dimarakis; Faisal Al-Allaf; Hanane M'Hamdi; Tamara Thalji; Jonathan P Welsh; Stephen B Marley; John Davies; Francesco Dazzi; Federica Marelli-Berg; Paul Tait; Raymond Playford; Long Jiao; Steen Jensen; Joanna P Nicholls; Ahmet Ayav; Mahrokh Nohandani; Farzin Farzaneh; Joop Gaken; Rikke Dodge; Malcolm Alison; Jane F Apperley; Robert Lechler; Nagy A Habib Journal: Stem Cells Date: 2006-03-23 Impact factor: 6.277