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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.
Affiliation
  • Bozzi A; Stanford Cardiovascular Institute, 265 Campus Drive, Rm G1120B, Stanford, CA 94305, USA; Instituto René Rachou, FIOCRUZ, Belo Horizonte, Brazil.
  • Sayed N; Stanford Cardiovascular Institute, 265 Campus Drive, Rm G1120B, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University, School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University, School of Medicine, Stanford, CA 94305
  • Matsa E; Stanford Cardiovascular Institute, 265 Campus Drive, Rm G1120B, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University, School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University, School of Medicine, Stanford, CA 94305
  • Sass G; Division of Infectious Diseases and Geographic Medicine, Stanford University, School of Medicine, Stanford, CA 94305, USA; California Institute for Medical Research, San Jose, CA 95128, USA.
  • Neofytou E; Stanford Cardiovascular Institute, 265 Campus Drive, Rm G1120B, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University, School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University, School of Medicine, Stanford, CA 94305
  • Clemons KV; Division of Infectious Diseases and Geographic Medicine, Stanford University, School of Medicine, Stanford, CA 94305, USA; California Institute for Medical Research, San Jose, CA 95128, USA.
  • Correa-Oliveira R; Instituto René Rachou, FIOCRUZ, Belo Horizonte, Brazil.
  • Stevens DA; Division of Infectious Diseases and Geographic Medicine, Stanford University, School of Medicine, Stanford, CA 94305, USA; California Institute for Medical Research, San Jose, CA 95128, USA.
  • Wu JC; Stanford Cardiovascular Institute, 265 Campus Drive, Rm G1120B, Stanford, CA 94305, USA; Department of Medicine, Division of Cardiovascular Medicine, Stanford University, School of Medicine, Stanford, CA 94305, USA; Department of Radiology, Stanford University, School of Medicine, Stanford, CA 94305
Stem Cell Reports ; 12(6): 1232-1241, 2019 06 11.
Article in En | MEDLINE | ID: mdl-31105048
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trypanosoma cruzi / Chagas Cardiomyopathy / Myocytes, Cardiac / Induced Pluripotent Stem Cells / Models, Biological Limits: Humans Language: En Journal: Stem Cell Reports Year: 2019 Document type: Article Affiliation country: Brazil
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Trypanosoma cruzi / Chagas Cardiomyopathy / Myocytes, Cardiac / Induced Pluripotent Stem Cells / Models, Biological Limits: Humans Language: En Journal: Stem Cell Reports Year: 2019 Document type: Article Affiliation country: Brazil