Abstract
Chagas disease discovered more than a century ago remains an incurable disease. The objective of this work was to investigate the therapeutic potential of cardiomyocytes derived from mouse embryonic stem cells (CM-mESC) in a model of chronic Chagasic cardiomyopathy (CCC). Mouse embryonic stem cells (mESC) were characterized, transduced with luciferase, and submitted to cardiac differentiation. CM-mESC were labeled with superparamagnetic iron oxide particles. To induce CCC, mice were infected with Brazil strain trypomastigotes. At 150 days post-infection (dpi), infected animals were treated with CM-mESC or PBS. Cells were detected by magnetic resonance imaging (MRI) and bioluminescence. Cardiac function was evaluated by MRI and electrocardiogram at 150 and 196 dpi. CCC mice showed significant differences in MRI and ECG parameters compared to non-infected mice. However, no differences were observed in contractile and electrical parameters between cell and PBS injected groups, 45 days after cell transplantation. Cells were detected 24 h after transplantation by MRI. CM-mESC bioluminescence tracking demonstrated over 90% decrease in signal 8 days after treatment. Nevertheless, the Infected + CM-mESC group showed a significant reduction in the percentage of collagen fibers when compared to the Infected + PBS group. In conclusion, CM-mESC therapy was not effective in reversing cardiac functional changes induced by Chagas disease despite some improvement in myocardial fibrosis.
Highlights
Chronic Chagasic cardiomyopathy (CCC) is caused by a protozoan parasite, Trypanosoma cruzi.In 1909 Carlos Chagas described the disease, identified the parasite and the transmission mode [1].Since thousands of papers have been published [2,3,4], but the physiopathology of the disease is still disputed
The mouse embryonic stem cell line E14TG2A generated at the University of Edinburg by Hooper et al [15] was kindly donated by Dr Henrique Marques Souza (University of Campinas, Campinas, SP, Brazil)
Since the exact time-point that separates the end of the acute phase and the beginning of the chronic Chagas disease is not well defined, we considered mice that survived as chronic
Summary
Chronic Chagasic cardiomyopathy (CCC) is caused by a protozoan parasite, Trypanosoma cruzi.In 1909 Carlos Chagas described the disease, identified the parasite and the transmission mode [1].Since thousands of papers have been published [2,3,4], but the physiopathology of the disease is still disputed. Chronic Chagasic cardiomyopathy (CCC) is caused by a protozoan parasite, Trypanosoma cruzi. In 1909 Carlos Chagas described the disease, identified the parasite and the transmission mode [1]. The disease has an acute and a chronic phase, sometimes separated by decades. The acute phase is usually asymptomatic or oligosymptomatic, and the chronic phase can include and indeterminate period, where the patient is asymptomatic or oligosymptomatic. Most infected patients remain in this indeterminate period, but 10–30% evolve to develop gastro-intestinal and/or cardiac symptoms. In Brazil, the cardiac form of the chronic disease is more common and is characterized by a dilated cardiomyopathy. Patients with CCC can develop fatal arrhythmias or progress to congestive heart failure (CHF), where the only possible therapy is heart transplantation [5]
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