Many Cells Make Life Work-Multicellularity in Stem Cell-Based Cardiac Disease Modelling

Area of Science:

• Cardiovascular Biology
• Stem Cell Biology
• Disease Modeling

Background:

• Cardiac disease is a leading cause of death globally, yet its progression remains poorly understood.
• Traditional in vitro models face limitations in replicating the myocardial microenvironment due to cell isolation challenges and in vitro functional changes.
• Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are emerging as a powerful tool to overcome these limitations.

Purpose of the Study:

• To review the historical development and current state of cardiac disease modeling using stem cell-derived cell types.
• To highlight the contribution of hiPSC-CMs in understanding cardiomyocyte (CM) and non-myocyte interactions in cardiac health and disease.
• To emphasize the potential of these models for future stem cell-based applications in complex cardiovascular dysfunctions.

Main Methods:

• Review of historical and current literature on stem cell-derived cardiac cell types for disease modeling.
• Focus on human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and their application.
• Analysis of studies investigating interactions between cardiomyocytes and non-myocyte components within the myocardial microenvironment.

Main Results:

• Stem cell technology, particularly hiPSC-CMs, has significantly advanced the ability to model cardiac microenvironments in vitro.
• These models facilitate the study of complex multicellular interactions between cardiomyocytes and non-myocytes (e.g., endothelial cells, fibroblasts, macrophages).
• Understanding these interactions is crucial for elucidating the pathogenesis of diseases like heart failure.

Conclusions:

• hiPSC-CMs offer unprecedented opportunities to investigate cardiomyocyte-non-myocyte crosstalk in cardiac health and disease.
• This technology is pivotal for advancing our knowledge of heart failure mechanisms and developing patient-specific disease models.
• Further development in this field is critical for realizing the full potential of stem cell-based cardiovascular research and therapeutics.