Bone marrow cell migration to the heart in a chimeric mouse model of acute chagasic disease

Abstract

BACKGROUND Chagas disease is a public health problem caused by infection with the protozoan Trypanosoma cruzi. There is currently no effective therapy for Chagas disease. Although there is some evidence for the beneficial effect of bone marrow-derived cells in chagasic disease, the mechanisms underlying their effects in the heart are unknown. Reports have suggested that bone marrow cells are recruited to the chagasic heart; however, studies using chimeric mouse models of chagasic cardiomyopathy are rare.OBJECTIVES The aim of this study was to investigate the migration of bone marrow cells to the heart after T. cruzi infection in a model of chagasic disease in chimeric mice.METHODS To obtain chimerical mice, wild-type (WT) C57BL6 mice were exposed to full body irradiation (7 Gy), causing bone marrow ablation. Then, bone marrow cells from green fluorescent protein (GFP)-transgenic mice were infused into the mice. Graft effectiveness was confirmed by flow cytometry. Experimental mice were divided into four groups: (i) infected chimeric (iChim) mice; (ii) infected WT (iWT) mice, both of which received 3 × 104 trypomastigotes of the Brazil strain; (iii) non-infected chimeric (Chim) mice; and (iv) non-infected WT mice.FINDINGS At one-month post-infection, iChim and iWT mice showed first degree atrioventricular block with decreased heart rate and treadmill exercise parameters compared to those in the non-infected groups.MAIN CONCLUSIONS iChim mice showed an increase in parasitaemia, myocarditis, and the presence of amastigote nests in the heart tissue compared to iWT mice. Flow cytometry analysis did not detect haematopoietic progenitor cells in the hearts of infected mice. Furthermore, GFP+ cardiomyocytes were not detected in the tissues of chimeric mice.

The Rising Role of Mesenchymal Stem Cells in the Treatment of Various Infectious Complications

“…Chagas disease, which is caused by the protozoan Trypanosoma cruzi, is endemic in Central and Latin America. However, incidence of the disease has recently increased in the United States of America, Canada, Japan, Australia, and Europe due to migratory movements [2,[90][91][92][93]. The disease has acute and chronic phases [90][91][92].…”

“…The available and future therapies of Chagas disease include: treatment of arrhythmias and heart failure, antiparasitic therapy, resynchronization treatment, heart transplantation, and stem cell therapies [2,90,91,93,95]. In patients with chronic Chagas CMP and cardiac failure, conventional pharmacologic therapies are limited by being not always effective, thus rendering the disease incurable [90,91,96].…”

“…Different stem cell types and delivery approaches have been used in both preclinical models as well as clinical trials with the aim of improving cardiac function and reversing complications [95]. In animal models, stem cell therapies have shown reductions in: right ventricular dilatation, and inflammatory infiltrates as well as fibrosis [91,93]. Stem cell therapy with BM-MSCs has emerged as a novel therapeutic option for Chagas CMP and heart failure [91,93].…”

“…In animal models, stem cell therapies have shown reductions in: right ventricular dilatation, and inflammatory infiltrates as well as fibrosis [91,93]. Stem cell therapy with BM-MSCs has emerged as a novel therapeutic option for Chagas CMP and heart failure [91,93]. In a murine model of Chagas disease, cotransplantation of autologous BM-MSCs and skeletal myoblasts has been shown to be effective in reversing ventricular dysfunction [94].…”

“…Transplantation of MSCs has shown clinical efficacy in animal or mouse models but studies in humans have not shown equivalent success due to a number of challenges that need to be overcome [2,91,93,95,98]. In animal models of chronic Chagas CMP, cardiac MSCs have been shown to exert protective effects by decreasing the degrees of fibrosis and inflammatory infiltrates in the affected myocardium [99].…”