Abstract 16165: Embryonic Stem Cell-derived Cardiomyocytes Increase Viable Myocardium but Do Not Improve Function in a Mouse Model of Chagasic Cardiomyopathy

Abstract

Chagas disease is a parasitic infection caused by Trypanosoma cruzi ( T. cruzi ). It is endemic in Latin America but cases have been increasing in the United States due to the migration of infected individuals. The objective of this work was to evaluate the effects of cell therapy with cardiomyocytes derived from mouse embryonic stem cells (CM-mESC) in a mouse model of chronic chagasic cardiomyopathy. CD1 mice were infected with the Brazil strain of T. cruzi . After 5 months, cardiac function was evaluated by magnetic resonance imaging (MRI) (Table 1). Left ventricular ejection fraction (LVEF) was decreased in infected animals when compared to non-infected controls, while LV end-diastolic volume (EDV) and LV end-systolic volume were increased. Right ventricular (RV) EF was not altered. However, RVEDV and RVESV were increased in the infected group when compared to non-infected animals. mESC E14TG2A line was differentiated into cardiomyocytes and efficiency was confirmed by troponin T staining. 8x10^5 CM-mESC were delivered by echocardiography-guided intramyocardial injection only if cardiomyocyte differentiation efficiency was above 70%. Cell tracking was performed by bioluminescence and MRI using luciferase-transduced cells and iron oxide nanoparticles, respectively. CM-mESC were detected in the heart for at least 8 days. After 45 days, MRI data showed no changes in LV or RV EF and volumes (Table 1). Sirius red staining was performed and the areas of viable myocardium and fibrosis were quantified by morphometry. Although no functional improvement was detected by MRI, there was a significant increase in viable myocardium when CM-mESC-treated mice were compared to placebo-treated animals. In conclusion, a single injection of CM-mESC in a mouse model of chagasic cardiomyopathy contributes to myocardial repair. However, this was insufficient to promote an improvement of cardiac function, which may require multiple cardiomyocyte injections.