In vitrocirculation model driven by tissue-engineered dome-shaped cardiac tissue

Area of Science:

• Cardiovascular Research
• Stem Cell Biology
• Biomaterials Engineering

Background:

• Three-dimensional cardiac tissues from cardiomyocytes are used for in vitro drug evaluation.
• Existing models lack the ability to simulate the human circulatory system.
• A functional, heart-like pump model is needed for advanced in vitro studies.

Purpose of the Study:

• To create a dome-shaped cardiac tissue using cell sheet stacking that mimics the heart's pump function.
• To evaluate the potential of this cardiac tissue to simulate the human circulatory system.
• To assess its utility in in vitro drug evaluation and as a biological pump.

Main Methods:

• Human induced pluripotent stem cells were differentiated into cardiomyocytes.
• Cardiomyocyte and fibroblast cell sheets were stacked and inflated into a dome shape.
• Cardiac tissue beating, stroke volume, pressure, and flow rate were measured.
• Pressure-volume diagrams were generated under varying fluidic resistance.

Main Results:

• A dome-shaped cardiac tissue (8 mm diameter) achieved autonomous beating and pump function.
• Stroke volume reached 21 ± 8.9 μl by day 21 and responded to stimulants.
• Pulsatile pressure reached 0.33 ± 0.048 mmHg, driving a flow rate of ~1 μl/s.
• The model generated pressure-volume diagrams, demonstrating its functional capacity.

Conclusions:

• The fabricated dome-shaped cardiac tissue successfully mimics heart pump function.
• This model can circulate culture medium, simulating the human circulatory system.
• It holds potential for use in multi-organ chips and for enhanced in vitro drug evaluation.