Project/Area Number |
14370774
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Human genetics
|
Research Institution | Niigata University |
Principal Investigator |
KAWADA Tomie Niigata University, Medical and Dental Hospital, Associate professor, 医歯学総合病院, 助教授 (00186107)
|
Co-Investigator(Kenkyū-buntansha) |
SATOH Hiroshi Niigata University, Medical and Dental Hospital, Professor, 医歯学総合病院, 教授 (10125768)
NAKAZAWA Mikio Niigata University, Faculty of Medicine, Professor, 医学部, 教授 (80143759)
TOYO-OKA Teruhiko Tokyo University Hospital, Faculty of Medicine, Professor, 医学部, 教授 (00146151)
|
Project Period (FY) |
2002 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥13,400,000 (Direct Cost: ¥13,400,000)
Fiscal Year 2004: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2003: ¥8,000,000 (Direct Cost: ¥8,000,000)
Fiscal Year 2002: ¥2,800,000 (Direct Cost: ¥2,800,000)
|
Keywords | cell transplantation / dilated cardiomyopathy / myoblast / cardiomyopathy hamster / myosine heavy chain / gene therapy / connexin-43 / 重症心不全 / δ-サルコグリガン / アデノ随伴ウイルス / δ-サルコグリカン / アデノ随伴ウイルスベクター |
Research Abstract |
The prognosis of patients with dilated eardiomyopathy(DCM) is still poor and cardiac transplantation is the most life-saving treatment in the advances cases. Cell transplantation is currently gaining evidence as a potential means of improving the prognosis of patients with heart failure. To treat DCM, we transplanted normal skeletal myoblast(SkM), to TO-2 strain hamsters, a representative model of human hereditary DCM, of which δ-sarcoglycan(SG) gene is deleted. We confirmed no rejection between TO-2 and golden hamsters by interchanging skin graft in the pilot study. SkM were isolated from the limbs of 3 weeks old normal golden hamsters. We transplanted SkM leveled to 5 weeks old TO-2 hearts. 4',6-Diamidino-2-phenylindole, dihydrochloride(DAPI) was used for nucleus staining, and 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate(DiI) was used for cell membrane staining. At 5 weeks after SkM transplantation, fast skeletal muscle type of skeletal muscle myosin heavy chain(fast-MHC) was detected by Western blotting analysis. DAPI and DiI positive cells were clearly detected in the left ventricle in the grafted TO-2. δ-SG, fast-and slow-MHC were immunologically stained in the grafted TO-2 hearts, but not in the control TO-2 hearts. Moreover, connexin-43 was expressed on the interface of cells that expressed δ-SG. These results suggest that SkM were successfully allografted to DCM hamster. These methods would provide a new strategy for the treatment of DCM.
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