Abstract
BackgroundChagas disease, resulting from infection with the parasite Trypanosoma cruzi (T. cruzi), is a major cause of cardiomyopathy in Latin America. Drug therapy for acute and chronic disease is limited. Stem cell therapy with bone marrow mesenchymal cells (MSCs) has emerged as a novel therapeutic option for cell death-related heart diseases, but efficacy of MSC has not been tested in Chagas disease.Methods and ResultsWe now report the use of cell-tracking strategies with nanoparticle labeled MSC to investigate migration of transplanted MSC in a murine model of Chagas disease, and correlate MSC biodistribution with glucose metabolism and morphology of heart in chagasic mice by small animal positron emission tomography (microPET). Mice were infected intraperitoneally with trypomastigotes of the Brazil strain of T. cruzi and treated by tail vein injection with MSC one month after infection. MSCs were labeled with near infrared fluorescent nanoparticles and tracked by an in vivo imaging system (IVIS). Our IVIS results two days after transplant revealed that a small, but significant, number of cells migrated to chagasic hearts when compared with control animals, whereas the vast majority of labeled MSC migrated to liver, lungs and spleen. Additionally, the microPET technique demonstrated that therapy with MSC reduced right ventricular dilation, a phenotype of the chagasic mouse model.ConclusionsWe conclude that the beneficial effects of MSC therapy in chagasic mice arise from an indirect action of the cells in the heart rather than a direct action due to incorporation of large numbers of transplanted MSC into working myocardium.
Highlights
Chagas disease is a serious public health problem in all Latin American countries [1], where it is estimated that 15–16 million people are infected with the its causative agent, the parasite Trypanosoma cruzi (T. cruzi) [2]
In a mouse model of chronic chagasic cardiomyopathy (CCC) we have previously shown that mononuclear cells from the bone marrow decrease inflammation and fibrosis, reduce or reverse right ventricular dilation and significantly restore gene expression pattern to that of control, non-infected hearts [10,11,12]
Efficient Labeling of Mesenchymal Cells In Vitro By microscopy, we observed that all of the cells were labeled with X-Sight nanoparticles in vitro after 4 hours of incubation (Figure 1A-A0) and because of that we considered that it was not necessary to quantify the number of labeled cells
Summary
Chagas disease is a serious public health problem in all Latin American countries [1], where it is estimated that 15–16 million people are infected with the its causative agent, the parasite Trypanosoma cruzi (T. cruzi) [2]. Chronic Chagas heart disease is a progressive, fibrotic inflammatory cardiomyopathy that results in permanent heart damage [6]. This heart damage leads to dilation and cardiac arrhythmia, and to congestive heart failure, which is the primary cause of death in chronic. For more than 40 years, the only treatment option for Chagas disease in the acute phase has been the anti-parasitic drugs nifurtimox and benznidazole. These drugs have side effects and lead to parasite resistance [9]. Chagas disease, resulting from infection with the parasite Trypanosoma cruzi (T. cruzi), is a major cause of cardiomyopathy in Latin America. Stem cell therapy with bone marrow mesenchymal cells (MSCs) has emerged as a novel therapeutic option for cell death-related heart diseases, but efficacy of MSC has not been tested in Chagas disease
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