Engineered Cardiac Microtissue Biomanufacturing Using Human Induced Pluripotent Stem Cell Derived Epicardial Cells

Area of Science:

• Cardiovascular Biology
• Stem Cell Biology
• Tissue Engineering

Background:

• Epicardial cells are essential for human heart development and in vitro cardiac tissue models.
• Induced pluripotent stem cells offer a renewable source for generating human epicardial cells.
• Studying epicardium development and function is challenging due to accessibility limitations.

Approach:

• Small molecule modulation of Wnt signaling was used to derive epicardial cells from induced pluripotent stem cells.
• Characterization of cell populations included WT1 expression, morphology, and passaging effects.
• 3D microtissue formation and co-culture with cardiomyocytes were assessed to evaluate functional properties.

Key Points:

• A robust population of epicardial cells (approx. 87.7% WT1+) was generated.
• Cell expansion in vitro showed limitations, with larger cell size and decreased cell number over passages.
• Low-passage epicardial cells formed more robust 3D microtissues compared to high-passage cells.
• Two distinct morphologic subpopulations were observed, including larger, migratory cells.
• Epicardial cells enhanced cardiac tissue remodeling and migration in co-culture without impairing cardiomyocyte function.

Conclusions:

• Stem cell-derived epicardial cells can be reliably generated and characterized.
• Early-passage epicardial cells are optimal for fabricating consistent engineered cardiac tissues.
• These findings advance the potential of stem cell-derived epicardial cells for cardiac modeling and biomanufacturing.