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https://www.arca.fiocruz.br/handle/icict/34923
USING HUMAN INDUCED PLURIPOTENT STEM CELL-DERIVED CARDIOMYOCYTES AS A MODEL TO STUDY TRYPANOSOMA CRUZI INFECTION
Trypanosoma cruzi
Chagas disease
cardiomyopathy
disease modeling
drug screening
Author
Affilliation
Stanford Cardiovascular Institute. Stanford, CA, USA/Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Stanford Cardiovascular Institute. Stanford, CA, USA/Department of Medicine. Division of Cardiovascular Medicine. Stanford University. School of Medicine., Stanford, CA, USA/Department of Radiology. Stanford University. School of Medicine. Stanford, CA, USA
Stanford Cardiovascular Institute. Stanford, CA, USA/Department of Medicine. Division of Cardiovascular Medicine. Stanford University. School of Medicine., Stanford, CA, USA/Department of Radiology. Stanford University. School of Medicine. Stanford, CA, USA
Division of Infectious Diseases and Geographic Medicine. Stanford University. School of Medicine, Stanford, CA, USA/California Institute for Medical Research. San Jose, CA, USA
Stanford Cardiovascular Institute. Stanford, CA, USA/Department of Medicine. Division of Cardiovascular Medicine. Stanford University. School of Medicine., Stanford, CA, USA/Department of Radiology. Stanford University. School of Medicine. Stanford, CA, USA
Division of Infectious Diseases and Geographic Medicine. Stanford University. School of Medicine, Stanford, CA, USA/California Institute for Medical Research. San Jose, CA, USA
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Division of Infectious Diseases and Geographic Medicine. Stanford University. School of Medicine, Stanford, CA, USA/California Institute for Medical Research. San Jose, CA, USA
Stanford Cardiovascular Institute. Stanford, CA, USA/Department of Medicine. Division of Cardiovascular Medicine. Stanford University. School of Medicine., Stanford, CA, USA/Department of Radiology. Stanford University. School of Medicine. Stanford, CA, USA
Stanford Cardiovascular Institute. Stanford, CA, USA/Department of Medicine. Division of Cardiovascular Medicine. Stanford University. School of Medicine., Stanford, CA, USA/Department of Radiology. Stanford University. School of Medicine. Stanford, CA, USA
Stanford Cardiovascular Institute. Stanford, CA, USA/Department of Medicine. Division of Cardiovascular Medicine. Stanford University. School of Medicine., Stanford, CA, USA/Department of Radiology. Stanford University. School of Medicine. Stanford, CA, USA
Division of Infectious Diseases and Geographic Medicine. Stanford University. School of Medicine, Stanford, CA, USA/California Institute for Medical Research. San Jose, CA, USA
Stanford Cardiovascular Institute. Stanford, CA, USA/Department of Medicine. Division of Cardiovascular Medicine. Stanford University. School of Medicine., Stanford, CA, USA/Department of Radiology. Stanford University. School of Medicine. Stanford, CA, USA
Division of Infectious Diseases and Geographic Medicine. Stanford University. School of Medicine, Stanford, CA, USA/California Institute for Medical Research. San Jose, CA, USA
Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brazil
Division of Infectious Diseases and Geographic Medicine. Stanford University. School of Medicine, Stanford, CA, USA/California Institute for Medical Research. San Jose, CA, USA
Stanford Cardiovascular Institute. Stanford, CA, USA/Department of Medicine. Division of Cardiovascular Medicine. Stanford University. School of Medicine., Stanford, CA, USA/Department of Radiology. Stanford University. School of Medicine. Stanford, CA, USA
Abstract
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.
Keywords
induced pluripotent stem cellsTrypanosoma cruzi
Chagas disease
cardiomyopathy
disease modeling
drug screening
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