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

肝细胞生长因子基因治疗急性移植物抗宿主病

• 批准号: 11671019
• 负责人: IWASAKI Tsuyoshi
• 金额: $ 2.24万
• 依托单位: HYOGO COLLEGE OF MEDICINE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671019/
• 关键词: GVHD; HGF; gene therapy; extramedullary hematopoiesis; HVJ-liposome; GVL effect; immune reconstitution; 免疫再核築

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.

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。

项目成果

Takanori Kuroiwa: "Hepatocyte growth factor ameliorates acute graft-versus-host Disease and promotes hematopoietic function"The Journal of Clinical Investigation. 107. 1365-1373 (2001)

Takanori Kuroiwa：“肝细胞生长因子可改善急性移植物抗宿主病并促进造血功能”《临床研究杂志》。

Takanori Kuroiwa et al.: "Hepatocyte growth factor ameliorates acute graft-versus-host disease and promotes hematopoietic function"The Journal of Clinical Investigation. 107. 1365-1373 (2001)

Takanori Kuroiwa 等人：“肝细胞生长因子可改善急性移植物抗宿主病并促进造血功能”《临床研究杂志》。

Takanori Kuroiwa et al.: "Hepatocyte growth factor ameliorates acute graft-verus-hast disease and promotes hematipoietic function"The Journal of Clinical Investigation. 107. 1365-1373 (2001)

Takanori Kuroiwa 等人：“肝细胞生长因子可改善急性移植物抗病毒病并促进造血功能”《临床研究杂志》。