重症心不全に対する治療戦略

Abstract

Regards to the therapy for end-stage failing heart, the heart transplantation is the only effective treatment but is still limited by donor shortage. Therefore, a novel strategy for myocardial regeneration are desired. Cell transplantation as a new approach to restore impaired heart still has several problems. Recently, we have developed cell sheet implantation to impaired heart. Therefore, we hypothesized that a tissue engineered contractile cardiomyocyte sheets may promise myocardial regeneration in the impaired myocardial injury.‹Experiment 1› Two weeks after Left anterior descending (LAD) ligation, two different treatments were conducted; 30 rats were divided into three groups; cardiomyocytes sheets implantation (T group, n=10), fibroblast sheets implantation (F group, n=10) and the control group with no treatment (C group, n=10). Cardiomyocyte sheets attached on the infarct myocardium in alignment and seemed to be homogeneous tissue in the myocardium. And immunohistochemical stain demonstrated neoangiogenesis and randomly oriented Connexin 43 in implanted cardiomyocyte sheets.‹Experiment 2› We constructed autologous myoblast sheets by the same method as cardiomyocyte sheets and implanted to the infarct myocardium. Myoblast sheets showed attachment to myocardium with angiogenesis. Systolic function was significantly higher in the myoblast sheet group. Histology revealed greater cellularity without scar formation and reduction of LV dilatation due to significant thickened wall.In conclusion, cardiomyocyte sheets integrated the impaired myocardium and improved cardiac performance. Thus, the contractile cardiomyocyte sheets may potentially regenerate the impaired myocardium.