Hepatocyte growth factor gene therapy of acute graft-versus-host disease

1.在骨骼肌中反复转染人肝细胞生长因子（HGF） CDNA可抑制肠上皮细胞凋亡和供体t细胞向肝脏的浸润，从而改善急性移植物抗宿主病（GVHD）引起的肠病和肝损伤。HGF基因转染可抑制小肠和肝脏中IFN-y和TNF-a的表达，降低血清IL-12.3。供体细胞髓外造血功能增强，转染HGF基因可提高GVHD小鼠的存活率。HGF基因转染不影响供体T细胞对宿主抗原的反应（混合淋巴细胞反应，CTL活性），从而促进GVHD小鼠的无白血病生存（HGF基因治疗将急性GVHD从移植物抗白血病效应中分离出来）。HGF基因转染促进造血干细胞来源的供体T细胞的免疫重建。

1.Repeated transfection of the human hepatocyte growth factor (HGF) CDNA into skeletal muscle inhibited apoptosis of intestinal epithelial cells and donor T-cell infiltration into the liver, thereby ameliorating the enteropathy and liver injury caused by acute graft-versus-host disease (GVHD).2.HGF gene transfection suppressed IFN-y and TNF-a expression the intestine and liver and decreased the serum IL-12.3.Extramedullary hematopoiesis by donor cells was increased, and the survival rate of GVHD mice was improved by HGF gene transfection.4.HGF gene transfection did not affect donor T cell responses to host antigens (mixed lymphocyte reaction, CTL activity), thereby promoting leukemia-free survival of GVHD mice (HGF gene therapy separated acute GVHD from graft-versus-leukemia effects).5.HGF gene transfection promoted immune reconstitution by hematopoietic stem cell-derived donor T cells.