Role of Cell Transplantation in Treating Heart Failure

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Cell transplantation is a promising strategy for treating heart failure. Research has demonstrated that some types of cells, such as skeletal myoblasts, survive and differentiate after grafting into the myocardium, and this is associated with improved cardiac function in experimental heart failure models. This has prompted the transplantation of these cells into the myocardium of humans in an attempt to establish safety and efficiency. We strongly believe that the future success of the therapy critically depends on resolving several fundamental issues by laboratory research. These include unclear mechanisms of the therapeutic effects achieved by this strategy and inadequate graft quality. The proposed research aims to investigate various aspects of graft behaviour in a cardiac environment, such as death/survival, proliferation, differentiation, integration and interaction between two kinds of muscle cells at genetic, molecular and cellular levels. The specific aims are: [1] study of cell-migration from the intra-vascular to the myocardial interstitial space following intra-coronary infusion; [2] investigation of detailed graft survival, proliferation and the causes of death; [3] attempt to improve graft survival with physical (heat shock), pharmacological (SOD, anti-cytokine antibody) and genetic (Bcl-2) procedures; [4] study of gap junction formation between skeletal myoblasts and cardiomyocytes in vitro co-culture system and in vivo cell transplantation; [5] evaluation of the effect of connexin 43 overexpression on gap junction formation between the two types of cells; [6] investigation of differentiation and possible phenotype modulation (skeletal to cardiac) of the skeletal graft; [7] study of interacting influence of the graft on the native myocardium; [8] investigation of the effect of overexpression of IL-1 receptor antagonist on attenuating remodelling in failing hearts and enhancing cell transplantation effects.