Cardiomyopathy phenotypes in human-induced pluripotent stem cell-derived cardiomyocytes-a systematic review

Area of Science:

• Cardiovascular Research
• Stem Cell Biology
• Genetics

Background:

• Human-induced pluripotent stem cells (hiPSC) are valuable for modeling cardiac diseases in a human context.
• Cardiomyopathies, including hypertrophic (HCM) and dilated (DCM) forms, represent significant cardiovascular health challenges.
• Understanding disease-specific phenotypes in hiPSC-derived cardiomyocytes (hiPSC-CM) is crucial for advancing research.

Purpose of the Study:

• To evaluate published data for defining in vitro HCM and DCM hiPSC-CM phenotypes.
• To compare findings with existing hypotheses on cardiomyopathy pathophysiology.
• To identify consistent and divergent cellular and molecular characteristics between HCM and DCM hiPSC-CM.

Main Methods:

• Systematic review of 38 studies investigating HCM and DCM using hiPSC-derived cardiomyocytes.
• Analysis of reported data on cell size, nuclear factor of activated T cells (NFAT) localization, gene expression (e.g., β-myosin heavy chain, NPPA/NPPB), and contractility.
• Contextualization of findings with current understanding of HCM/DCM dysfunction.

Main Results:

• HCM hiPSC-CM showed larger cell size, increased nuclear NFAT localization, and higher β-myosin heavy chain expression compared to controls.
• DCM hiPSC-CM exhibited consistently reduced force development.
• Both HCM and DCM lines frequently displayed sarcomere disorganization, elevated NPPA/NPPB levels, and arrhythmogenic beating.

Conclusions:

• Current data suggest potential disease-specific in vitro phenotypes for HCM and DCM hiPSC-CM.
• Significant data scatter and limited use of isogenic controls necessitate caution in interpretation.
• Further systematic, quantitative studies with high-content assays are required to solidify these findings and advance the field.