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

Area of Science:

• Cardiology
• Parasitology
• Stem Cell Biology

Background:

• Chagas disease (ChD) is a neglected tropical disease.
• Cardiomyopathy is the primary cause of mortality in patients infected with Trypanosoma cruzi.
• The heart is a key target organ in Chagas disease pathogenesis due to parasite replication in cardiomyocytes (CMs).

Purpose of the Study:

• To develop and utilize a human induced pluripotent stem cell-derived CM (iPSC-CM) model to investigate the pathogenesis of Chagas disease.
• To understand the intricate interactions between Trypanosoma cruzi and host cardiac cells.

Main Methods:

• Modeling Chagas disease using human iPSC-CMs infected with the T. cruzi Y strain.
• Characterization of infected iPSC-CMs, including identification of all parasite life cycle stages.
• Analysis of host cell responses, including gene expression profiling, cell contractility assessment, and examination of cardiac marker distribution.

Main Results:

• Successful infection of iPSC-CMs with T. cruzi, with all parasite stages observed.
• Significant alterations in gene expression, cell contractility, and cardiac marker distribution in infected iPSC-CMs.
• Induction of a pro-inflammatory profile in infected iPSC-CMs, evidenced by elevated cytokine and cell-trafficking regulator levels.

Conclusions:

• The iPSC-CM model effectively recapitulates key aspects of Chagas disease in cardiac cells.
• Infected iPSC-CMs exhibit significant pathological changes and a pro-inflammatory response.
• This iPSC-CM model serves as a valuable platform for exploring novel therapeutic strategies for Chagas disease.