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Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model to Study Trypanosoma cruzi Infection
Chagas disease (ChD) is one of the most neglected tropical diseases, with cardiomyopathy being the main cause of death in Trypanosoma cruzi-infected patients. As the parasite actively replicates in cardiomyocytes (CMs), the heart remains a key target organ in the pathogenesis of ChD. Here we modeled...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565757/ https://www.ncbi.nlm.nih.gov/pubmed/31105048 http://dx.doi.org/10.1016/j.stemcr.2019.04.017 |
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author | Bozzi, Adriana Sayed, Nazish Matsa, Elena Sass, Gabriele Neofytou, Evgenios Clemons, Karl V. Correa-Oliveira, Rodrigo Stevens, David A. Wu, Joseph C. |
author_facet | Bozzi, Adriana Sayed, Nazish Matsa, Elena Sass, Gabriele Neofytou, Evgenios Clemons, Karl V. Correa-Oliveira, Rodrigo Stevens, David A. Wu, Joseph C. |
author_sort | Bozzi, Adriana |
collection | PubMed |
description | Chagas disease (ChD) is one of the most neglected tropical diseases, with cardiomyopathy being the main cause of death in Trypanosoma cruzi-infected patients. As the parasite actively replicates in cardiomyocytes (CMs), the heart remains a key target organ in the pathogenesis of ChD. Here we modeled ChD using human induced pluripotent stem cell-derived CMs (iPSC-CMs) to understand the complex interplay between the parasite and host cells. We showed that iPSC-CMs can get infected with the T. cruzi Y strain and that all parasite cycle stages can be identified in our model system. Importantly, characterization of T. cruzi-infected iPSC-CMs showed significant changes in their gene expression profile, cell contractility, and distribution of key cardiac markers. Moreover, these infected iPSC-CMs exhibited a pro-inflammatory profile as indicated by significantly elevated cytokine levels and cell-trafficking regulators. We believe our iPSC-CM model is a valuable platform to explore new treatment strategies for ChD. |
format | Online Article Text |
id | pubmed-6565757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-65657572019-06-20 Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model to Study Trypanosoma cruzi Infection Bozzi, Adriana Sayed, Nazish Matsa, Elena Sass, Gabriele Neofytou, Evgenios Clemons, Karl V. Correa-Oliveira, Rodrigo Stevens, David A. Wu, Joseph C. Stem Cell Reports Report Chagas disease (ChD) is one of the most neglected tropical diseases, with cardiomyopathy being the main cause of death in Trypanosoma cruzi-infected patients. As the parasite actively replicates in cardiomyocytes (CMs), the heart remains a key target organ in the pathogenesis of ChD. Here we modeled ChD using human induced pluripotent stem cell-derived CMs (iPSC-CMs) to understand the complex interplay between the parasite and host cells. We showed that iPSC-CMs can get infected with the T. cruzi Y strain and that all parasite cycle stages can be identified in our model system. Importantly, characterization of T. cruzi-infected iPSC-CMs showed significant changes in their gene expression profile, cell contractility, and distribution of key cardiac markers. Moreover, these infected iPSC-CMs exhibited a pro-inflammatory profile as indicated by significantly elevated cytokine levels and cell-trafficking regulators. We believe our iPSC-CM model is a valuable platform to explore new treatment strategies for ChD. Elsevier 2019-05-16 /pmc/articles/PMC6565757/ /pubmed/31105048 http://dx.doi.org/10.1016/j.stemcr.2019.04.017 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Report Bozzi, Adriana Sayed, Nazish Matsa, Elena Sass, Gabriele Neofytou, Evgenios Clemons, Karl V. Correa-Oliveira, Rodrigo Stevens, David A. Wu, Joseph C. Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model to Study Trypanosoma cruzi Infection |
title | Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model to Study Trypanosoma cruzi Infection |
title_full | Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model to Study Trypanosoma cruzi Infection |
title_fullStr | Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model to Study Trypanosoma cruzi Infection |
title_full_unstemmed | Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model to Study Trypanosoma cruzi Infection |
title_short | Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model to Study Trypanosoma cruzi Infection |
title_sort | using human induced pluripotent stem cell-derived cardiomyocytes as a model to study trypanosoma cruzi infection |
topic | Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565757/ https://www.ncbi.nlm.nih.gov/pubmed/31105048 http://dx.doi.org/10.1016/j.stemcr.2019.04.017 |
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