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.