Transplantation of bone marrow-derived stem cells into heart tissue in dilated cardiomyopathy hamster

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570700
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kyoto Women's University
• Principal Investigator: FUJIWARA Takako Kyoto Women's University, Department of Food Science, Professor, 家政学部, 教授 (80111897)
• Project Period (FY): 2002 – 2003
• Keywords: Cardiomyopathy / G-CSF / UM-X7.1 hamster / Heart failure / Autophagy

Research Abstract

Granulocyte colony-stimulating factor (G-CSF) reportedly stimulates translocation of bone marrow cells into infarcted heart tissue, where they subsequently differentiate into cardiomyocytes, thereby exerting beneficial effects on postinfarction ventricular remodeling and heart function. Whether G-CSF would exert similar effects on hearts with failure of nonischemic origin-e.g., dilated cardiomyopathy (DCM)-remain unknown. UM-X7.1 hamsters are an animal model of human DCM. Beginning at 15 weeks of age, male UM-X7.1 hamsters were subcutaneously injected with G-CSF (10μg/kg/day) 5 days/week for 15 weeks (n=16). A control group (n=15) received an equal volume of distilled water. The G-CSF therapy markedly increased the survival rate among 30-week-old hamsters (100% vs.53%, p<0.0001). This increased survival rate was associated with significantly reduced ventricular enlargement and fibrosis and improved ventricular function (measured in terms of ejection fraction, left ventricular end-diastolic pressure, and ±dp/dt) ; reduced autophagy-like degeneration/death of cardiomyocytes ; decreased membrane permeability (measured in terms of Evans blue uptake) ; downregulation of the cardiotoxic cytokine tumor necrosis factor α-(TNF-α) ; and upregulation of matrix metalloproteinase-2 (MMP-2) and MMP-9 catalytic activity.
Moreover, confocal microscopy revealed translocation of a relatively small number of bone marrow cells into the myocardium, which then expressed the cardiomyocyte phenotype. In conclusion, G-CSF significantly improves survival rates and cardiac function in an animal model of DCM, suggesting that G-CSF administration may represent a new approach to the prevention of heart failure development resulting from nonischemic cardiomyopathy.