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

Abstract

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