Generation of a human iPSC-derived cardiomyocyte/fibroblast engineered heart tissue model

Area of Science:

• Cardiovascular Research
• Stem Cell Biology
• Biomedical Engineering

Background:

• Animal models face limitations due to species-specific physiology, hindering cardiac disease research.
• Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) show promise for cardiac modeling but lack full maturity.
• 3D stem cell-derived cardiac models aim to replicate the heart's complex microenvironment in vitro.

Purpose of the Study:

• To develop efficient protocols for differentiating hiPSC-CMs and hiPSC-CFs.
• To create physiologically relevant 3D engineered heart tissue (EHT) models incorporating both cell types.
• To investigate the impact of hiPSC-CFs on hiPSC-CM function within EHTs and their potential to replace animal models.

Main Methods:

• Efficient differentiation protocols for hiPSC-CMs and hiPSC-CFs were established.
• hiPSC-CMs and hiPSC-CFs were integrated into 3D engineered heart tissue (EHT) models.
• The structure and function of EHTs composed of hiPSC-CMs alone versus hiPSC-CMs with hiPSC-CFs were analyzed.

Main Results:

• Engineered heart tissues (EHTs) incorporating both hiPSC-CMs and hiPSC-CFs demonstrated slower beating frequencies.
• EHTs with both cell types exhibited enhanced contractile force compared to hiPSC-CMs alone.
• The inclusion of hiPSC-CFs better recapitulated cell-to-cell and cell-to-matrix interactions.

Conclusions:

• Integrating hiPSC-CFs into hiPSC-CM EHTs creates a more accurate in vitro model of cardiac tissue.
• These advanced 3D models can elucidate the interplay between cardiac cell types and their role in fibrosis.
• This approach holds significant potential for reducing reliance on animal models in cardiac disease research.