Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model to Study Trypanosoma cruzi Infection
| Autor: | Karl V. Clemons, Elena Matsa, David A. Stevens, Nazish Sayed, Gabriele Sass, Adriana Bozzi, Joseph C. Wu, Rodrigo Correa-Oliveira, Evgenios Neofytou |
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| Rok vydání: | 2019 |
| Předmět: |
Chagas Cardiomyopathy
0301 basic medicine Chagas disease Trypanosoma cruzi medicine.medical_treatment Induced Pluripotent Stem Cells Cardiomyopathy Models Biological Biochemistry Pathogenesis 03 medical and health sciences 0302 clinical medicine Report health services administration Gene expression Genetics medicine Humans Myocytes Cardiac Induced pluripotent stem cell lcsh:QH301-705.5 health care economics and organizations lcsh:R5-920 biology Cell Biology medicine.disease biology.organism_classification 030104 developmental biology Cytokine lcsh:Biology (General) Immunology Trypanosoma lcsh:Medicine (General) 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Stem Cell Reports, Vol 12, Iss 6, Pp 1232-1241 (2019) |
| ISSN: | 2213-6711 |
| DOI: | 10.1016/j.stemcr.2019.04.017 |
| Popis: | Summary: 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. : In this article, Wu and colleagues demonstrate for the first time that human induced pluripotent stem cell-derived cardiomyocytes could be used as a platform to model Chagas disease. By studying the effects of T. cruzi on iPSC-CMs, we intend to understand the complex interplay between the parasite and the host cells, which could allow exploration of new treatment strategies. Keywords: induced pluripotent stem cells, Trypanosoma cruzi, Chagas disease, cardiomyopathy, disease modeling, drug screening |
| Databáze: | OpenAIRE |
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