Bioengineering an electro-mechanically functional miniature ventricular heart chamber from human pluripotent stem...

Area of Science:

• Biomaterials science
• Stem cell biology
• Cardiovascular research

Background:

• Existing in vitro models lack direct cardiac pump performance measures.
• A gap exists between animal models and human clinical trials for cardiac research.

Purpose of the Study:

• To engineer a next-generation in vitro biomimetic model of a pumping human heart chamber.
• To demonstrate its utility for pharmaceutical testing and drug discovery.

Main Methods:

• Engineered a 3D cardiac organoid chamber (hvCOC) from human pluripotent stem cell-derived ventricular cardiomyocytes (hvCM).
• Utilized a collagen-based extracellular matrix hydrogel for embedding cells.
• Performed structural, transcriptomic (RNA-seq), and physiological (contractile and electrophysiological) analyses.

Main Results:

• The hvCOC model exhibited organized sarcomeres and myofibrillar microstructures.
• Key cardiac-specific proteins and Ca2+ handling genes were upregulated compared to simpler cultures.
• The model accurately measured contractile parameters (ejection fraction, pressure) and electrophysiological properties (action potential, conduction velocity).
• Demonstrated predictable responses to pharmacological interventions (inotropes).

Conclusions:

• The engineered human ventricle-like cardiac organoid chamber (hvCOC) mimics native ventricle characteristics.
• This 'human-heart-in-a-jar' technology provides human-specific preclinical data.
• Facilitates early-stage drug discovery by improving pharmaceutical testing accuracy.