Therapy with Cardiomyocytes Derived from Pluripotent Cells in Chronic Chagasic Cardiomyopathy

Brasil, Guilherme Visconde; Silva dos Santos, Danúbia; Mendonça, Elias Ataide; Mesquita, Fernanda Cristina Paccola; Kasai-Brunswick, Tais Hanae; Cunha, Sandro Torrentes da; Pimentel, Cibele Ferreira; Vasconcelos-dos-Santos, Andréia de; Mendez-Otero, Rosália; Azevedo Filho, Clério Francisco de; Goldenberg, Regina Coeli dos Santos; Campos de Carvalho, Antonio Carlos

doi:10.3390/cells9071629

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Therapy with Cardiomyocytes Derived from Pluripotent Cells in Chronic Chagasic Cardiomyopathy

Guilherme Visconde Brasil

^1,†

Danúbia Silva dos Santos

^1,†

Elias Ataide Mendonça

¹,

Fernanda Cristina Paccola Mesquita

Tais Hanae Kasai-Brunswick

^1,2,3,

Sandro Torrentes da Cunha

¹,

Cibele Ferreira Pimentel

¹,

Andréia de Vasconcelos-dos-Santos

¹,

Rosália Mendez-Otero

^1,3,

Clério Francisco de Azevedo Filho

⁴

Regina Coeli dos Santos Goldenberg

^1,3 and

Antonio Carlos Campos de Carvalho

^1,2,3,*

Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro-RJ 21941-902, Brazil

National Center for Structural Biology and Bioimaging - CENABIO, Federal University of Rio de Janeiro, Rio de Janeiro-RJ 21941-902, Brazil

National Institute of Science and Technology for Regenerative Medicine-REGENERA, Federal University of Rio de Janeiro, Rio de Janeiro-RJ 21941-902, Brazil

⁴

D’Or Institute for Research and Education, Rio de Janeiro, Rio de Janeiro-RJ 22281-100, Brazil

Author to whom correspondence should be addressed.

^†

These authors have contributed equally to this work.

Cells 2020, 9(7), 1629; https://doi.org/10.3390/cells9071629

Received: 8 June 2020 / Revised: 30 June 2020 / Accepted: 2 July 2020 / Published: 7 July 2020

(This article belongs to the Special Issue Stem Cell-Immune Function and Cardiac Regeneration)

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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. View Full-Text

Keywords: Chagas disease; cell therapy; embryonic stem cell; cardiomyocytes; chronic Chagasic cardiomyopathy

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Brasil, G.V.; Silva dos Santos, D.; Mendonça, E.A.; Mesquita, F.C.P.; Kasai-Brunswick, T.H.; Cunha, S.T.d.; Pimentel, C.F.; Vasconcelos-dos-Santos, A.d.; Mendez-Otero, R.; Azevedo Filho, C.F.d.; Goldenberg, R.C.d.S.; Campos de Carvalho, A.C. Therapy with Cardiomyocytes Derived from Pluripotent Cells in Chronic Chagasic Cardiomyopathy. Cells 2020, 9, 1629. https://doi.org/10.3390/cells9071629

AMA Style

Brasil GV, Silva dos Santos D, Mendonça EA, Mesquita FCP, Kasai-Brunswick TH, Cunha STd, Pimentel CF, Vasconcelos-dos-Santos Ad, Mendez-Otero R, Azevedo Filho CFd, Goldenberg RCdS, Campos de Carvalho AC. Therapy with Cardiomyocytes Derived from Pluripotent Cells in Chronic Chagasic Cardiomyopathy. Cells. 2020; 9(7):1629. https://doi.org/10.3390/cells9071629

Chicago/Turabian Style

Brasil, Guilherme Visconde, Danúbia Silva dos Santos, Elias Ataide Mendonça, Fernanda Cristina Paccola Mesquita, Tais Hanae Kasai-Brunswick, Sandro Torrentes da Cunha, Cibele Ferreira Pimentel, Andréia de Vasconcelos-dos-Santos, Rosália Mendez-Otero, Clério Francisco de Azevedo Filho, Regina Coeli dos Santos Goldenberg, and Antonio Carlos Campos de Carvalho. 2020. "Therapy with Cardiomyocytes Derived from Pluripotent Cells in Chronic Chagasic Cardiomyopathy" Cells 9, no. 7: 1629. https://doi.org/10.3390/cells9071629

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