Chagas disease is caused by the hemoflagelate parasite Trypanosoma cruzi About 30% of infected individuals develop the cardiac form of the disease, usually decades after the primary infection Cardiac Chagasic patients present cardiomegaly, electrical and mechanical disturbances of heart function. The disease evolutes to congestive heart failure and the only currently available therapy is heart transplantation. Performing heart transplants in chagasic patients is not only expensive, but also difficult, as immunosuppressive drugs can bring about patent parasitemia due to persistent parasitism in the chronic phase of infection. The major objective of this proposal is to develop an alternative and efficient therapeutical procedure for chronic chagasic cardiomyophaty (CCC), based on transplantation of bone marrow derived stem cells. Murine models of CCC will allow quantification of heart inflammatory foci and degree of fibrosis in treated and untreated animals, using confocal microscopy and morphometric analysis. Functional analysis, performed by conventional electro and ecocardiography will also be performed. Use of syngeneic-labelled bone marrow stem cells, obtained by transfection with fluorescent proteins or from transgenic mice, will permit identification and follow up of the differentiation of the transplanted cells in the heart of the recipient animal. In vitro culture and co-culture systems of cardiomyocytes and marrow stem cells will be used to gain a deeper insight into the signaling pathways that lead to differentiation of the marrow stem cells into cardiomyocytes, using DNA microarray systems. Immunologic repertoires of the treated mice will be compared to those of untreated, age matched infected animals, to evaluate the contribution of attenuation of autoimmune mechanisms to the proposed stem cell therapy.
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