title: Hepatocyte growth factor-modified mesenchymal stem cells improve ischemia/reperfusion-induced acute lung injury in rats.
abstract: Accumulative evidence demonstrated that mesenchymal stem cell (MSC) engraftment could protect tissue injury from ischemia/reperfusion (I/R). Hepatocyte growth factor (HGF) has important roles in the cell and tissue repairment and regeneration. Here we investigated the enhanced effects of HGF-modified MSCs on I/R-induced acute lung injury. Rat bone marrow-derived MSCs were successfully transfected to express HGF. HGF modification did not affect the characteristics of MSCs, and increased MSC viability, and inhibit the proinflammatory phenotype of MSCs in the inflammatory condition. In the rat model of I/R-induced lung injury, MSC-HGF engraftment attenuated lung wet-to-dry weight ratio, enhanced PaO2level and improved lung pathological injury, compared with MSC treatment. Moreover, the decreased acitivity of malondialdehyde, myeloperoxidase and tumor necrosis factor-α and increased superoxide dismutase content and interleukin-10 level were also observed in the MSC-HGF treatment, compared with the MSC group. Importantly, we found that HGF contributed to the survival of engrafted MSCs in the lung tissue through upregulation of Bcl-2 level and reduction of Caspase 3 activation. Thus our data show for the first time a clear beneficial effect of HGF gene modification on the survival of MSCs and enhanced improvement for I/R-induced lung injury.
authors.affiliation: Department of Thoracic Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.|Fujian Institute of Cardio-Thoracic Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Respiratory Diseases, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: School of Public Health, Fujian Medical University, Fuzhou, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.affiliation: Blood Bank, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Thoracic Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.|Fujian Institute of Cardio-Thoracic Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.
authors.forename: W
authors.initials: W
authors.lastname: Han
authors.affiliation: Department of Thoracic Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.|Fujian Institute of Cardio-Thoracic Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Thoracic Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.|Fujian Institute of Cardio-Thoracic Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.
authors.forename: M
authors.initials: M
authors.lastname: Kang
authors.affiliation: Fujian Institute of Cardio-Thoracic Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.|Department of Cardiac Surgery, The Affiliated Union Hospital, Fujian Medical University, Fuzhou, People's Republic of China.
authors.forename: L
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D015316:Genetic Therapy; D017228:Hepatocyte Growth Factor / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008168:Lung / Q000098:blood supply* / Q000378:metabolism; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D008315:Malondialdehyde; D017228:Hepatocyte Growth Factor; D009195:Peroxidase; D053148:Caspase 3