Cell therapies for Chagas disease Adriana Bastos Carvalho, Regina Coeli Dos Santos Goldenberg, Antonio Carlos Campos de Carvalho  Cytotherapy  DOI: 10.1016/j.jcyt.2017.07.014 Copyright © 2017 International Society for Cellular Therapy Terms and Conditions

Figure 1 Diagnosis and risk stratification in chronic chagasic cardiomyopathy. After Chagas disease diagnosis is confirmed, patients should be submitted to a 12-lead electrocardiogram. If results are normal, follow-up is recommended every 1–2 years. An altered electrocardiogram requires further investigation with chest radiograph, echocardiography and 24-h Holter monitoring. Low-risk patients: no symptoms or mild symptoms of HF (NYHA I or II), with normal chest radiograph, normal echocardiography and Holter without non-sustained ventricular tachycardia (NSVT). Intermediate risk patients: no symptoms or mild symptoms of HF (NYHA I or II), with normal chest radiograph, normal echocardiography and Holter with NSVT or enlarged heart on chest radiograph, cardiac dysfunction on echocardiography and Holter without NSVT. High-risk patients: no symptoms or mild symptoms of HF (NYHA I or II), with enlarged heart on chest radiograph, cardiac dysfunction on echocardiography and Holter with NSVT or moderate to severe symptoms of HF (NYHA III–IV). Adapted from Andrade et al. [4]. Cytotherapy DOI: (10.1016/j.jcyt.2017.07.014) Copyright © 2017 International Society for Cellular Therapy Terms and Conditions

Figure 2 Chagasic cardiomyopathy in mice. (A) Cardiac tissue stained with hematoxylin and eosin showing the presence of inflammatory cells in the heart. (B) Sirius red staining of cardiac tissue demonstrating fiber deposition. Echocardiography of noninfected (C) and infected (D) mice 7 months after infection. Yellow arrows indicate the limits of the crescent-shaped right ventricle. Magnetic resonance imaging of noninfected (E) and infected (F) mice 7 months after infection. Arrows indicate limits of the right (yellow) and left (red) ventricles; asterisks indentify the interventricular septum. Cytotherapy DOI: (10.1016/j.jcyt.2017.07.014) Copyright © 2017 International Society for Cellular Therapy Terms and Conditions

Figure 3 Timeline of the MiHeart clinical trial. Patients underwent clinical optimization during 60 days before the collection of baseline data on day 0 (D0). After 2 hours, cells were harvested from the bone marrow and patients underwent cardiac catheterization for inclusion/exclusion into the trial and cell/placebo injection. Patients were randomized into two groups: placebo and cell-treated and were submitted to endpoint evaluations at 6 months and one year after treatment. Adapted from Ribeiro Dos Santos et al. [42]. Cytotherapy DOI: (10.1016/j.jcyt.2017.07.014) Copyright © 2017 International Society for Cellular Therapy Terms and Conditions