| Co-Investigator(Kenkyū-buntansha) |
MIKAMI Taisei Hokkaido Univ., School of Med., Asso.Prof., 医学部, 助教授 (90250456)
SAWADA Kenichi Akita Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (90226069)
UEDA Toshimitsu Hokkaido Univ., Institute for Genetic Med., Prof., 遺伝子病制御研究所, 教授 (00160185)
OKAMOTO Hiroshi Hokkaido University, Hospital, Asso.Prof., 医学部・歯学部附属病院, 講師 (50260394)
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| Research Abstract |
Myocardial regeneration with hone marrow derived stem-cell transplantation is a possible treatment option to reverse the deleterious hemodynamic and neurohumoral effects that occur after myocardial infarction and can lead to heart failure. Various preclinical animal studies show the potential to regenerate myocardium and improve perfusion to the infarct area to improve cardiac function but also suggest that stem cells may have pro-arrhythmic effects. Thus, first to know whether stem cells potentially self-renew and differentiate into cardiomyocytes or endothelial cells, we examined the effects of bone marrow-mononuclear CD34 positive cell transplantation on remodeling process by using cardiomayopathic hamsters as a model for heart failure. Four weeks after cell transplantation, echocardiography revealed a significant, but not greater extent of improvement of % fractional shortening. Rather, long-term pharmacological intervention such as combined therapy with ACE inhibitor and ARB have elicited much more improved than cell transplantation. Second to establish the efficient system of cell implantation, large number of progenitor cells would be needed. However, GVHD may be problematic. Thus, we clarified the role of osteopontin in cardiac remodeling and developed CTLA4Ig or ICOSIg to prevent GVHD by cell transplantation. Thud, to know the mechanisms of cell transplantation, we examined expression changes in DNA by micro-tip analysis. Fourth, to know the clinical outcome, we investigated efficacy and safety of autologous implantation of hone marrow-mononuclear cells in patients with ischaemic limbs because of peripheral arterial disease. In the current study, bone marrow derived stem-cell transplantationis a promising strategy for heart failure, establishing the efficient delivery and evaluation systems would he needed.
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