| Project/Area Number |
13470274
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Thoracic surgery
|
|---|
| Research Institution | OSAKA UNIVERSITY |
|---|
Principal Investigator |
SAWA Yoshiki Osaka university graduate school of medicine, Associate professor, 医学部附属病院, 助教授 (00243220)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Toshiki Osaka university graduate school of medicine, Lecturer, 医学系研究科, 講師 (50263257)
FUKUSHIMA Norihide Osaka university graduate school of medicine, Assistant Professor, 医学系研究科, 助手 (30263247)
MATSUDA Hikaru Osaka university graduate school of medicine, Professor, 医学系研究科, 教授 (00028614)
TAKANO Hiroshi Osaka university graduate school of medicine, Assistant Professor, 医学系研究科, 助手 (70346196)
MIYAMOTO Yuji Osaka university graduate school of medicine, Lecturer, 医学系研究科, 講師 (80229898)
西村 元延 大阪大学, 医学系研究科, 助手 (90291442)
|
|---|
| Project Period (FY) |
2001 – 2002
|
| Project Status |
Completed (Fiscal Year 2002)
|
| Budget Amount *help |
¥16,600,000 (Direct Cost: ¥16,600,000)
Fiscal Year 2002: ¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 2001: ¥10,600,000 (Direct Cost: ¥10,600,000)
|
|---|
| Keywords | Severe heart failure / cellular cardiomyoplasty / Gene therapy / Combination therapy / Cellular vector / Circulatory Support / Adhesion molecule / Hepatocyte growth factor / 心筋再生 / 遺伝子導入 / Suicide gene therapy / 心筋梗塞 |
|---|
| Research Abstract |
[Exploitation of new cellular therapy using cellular cardiomyoplasty and gene transfection]
We used a ligation model of proximal left anterior descending coronary artery (LAD) of Lewis rats. Two weeks after LAD ligation, three different treatments were conducted; 1) neonatal rat cardiomyocytes group (T group), 2) HVJ-liposomes bearing the hHGF gene group (H group), and 3) combined (T-H group). The injection site was the scar area of myocardial infarction. For control, culture medium was injected (C group). Echocardiography demonstrated that cardiac performance was significantly ameliorated in the T-H group four and 8 weeks after injection. Contrast echocardiography also showed a marked increase in myocardial perfusion in the T-H group but not in the other groups. In the T-H group, neovascularization and a marked reduction of fibrosis were observed histologically. In an immunohistochemical study, strong staining for beta1-integrin, alpha- and beta-dystroglycan were found principally in the basement membrane of myocytes in the T-H group 8 weeks after transplantation, although there was weak immunoreactivity in the T group.
[Cellular vector and control release of growth factors]
Human HGF cDNA expression plasmid was permanently transfected into NIH3T3 (NIH/HGF). Then, TK was permanently transfected into NIH/HGF (NIH/HGF/TK). After LAD was ligated in the heart of SCID rat, four different materials were transplanted; 1) NIH/HGF , 2) NIH/HGF/TK, oral administration of GCV, 3) NIH3T3 , 4) culture medium (C group). In vitro study, proliferation of NIH/HGF/TK cells was well suppressed under GCV. In vivo study, significant increase of cardiac performance and angiogenesis were observed in the NIH/HGF and the NIH/HGF/TK group 4 weeks after transplantation. Although tumorous lesions were detected in the NIH/HGF group, their growth was completely controlled in the NIH/HGF/TK group.
|
