Using Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes as a Model to Study Trypanosoma cruzi Infection

Stem Cell Reports. 2019 Jun 11;12(6):1232-1241. doi: 10.1016/j.stemcr.2019.04.017. Epub 2019 May 16.

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: Chagas disease; Trypanosoma cruzi; cardiomyopathy; disease modeling; drug screening; induced pluripotent stem cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chagas Cardiomyopathy / metabolism*
  • Chagas Cardiomyopathy / pathology
  • Chagas Cardiomyopathy / therapy
  • Humans
  • Induced Pluripotent Stem Cells* / metabolism
  • Induced Pluripotent Stem Cells* / parasitology
  • Induced Pluripotent Stem Cells* / pathology
  • Models, Biological*
  • Myocytes, Cardiac* / metabolism
  • Myocytes, Cardiac* / parasitology
  • Myocytes, Cardiac* / pathology
  • Trypanosoma cruzi / metabolism*