A New Versatile Platform for Assessment of Improved Cardiac Performance in Human-Engineered Heart Tissues

Area of Science:

• Biomedical Engineering
• Stem Cell Biology
• Cardiovascular Research

Background:

• Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are valuable for in vitro heart disease modeling and drug screening.
• The immaturity of hPSC-CMs limits their application in current cardiac research.
• Developing functional, mature cardiac models is crucial for advancing cardiovascular research.

Purpose of the Study:

• To develop a platform for generating three-dimensional engineered heart tissues (EHTs) from hPSC-CMs.
• To measure the force of EHTs under mechanical and electrical stimulation.
• To optimize EHT maturation for enhanced functional performance and utility in research.

Main Methods:

• Generation of modular and versatile EHTs using hPSC-CMs in a 12-well plate format.
• Culturing and maintaining EHTs in different media, including a maturation medium with triiodothyronine, dexamethasone, and insulin-like growth factor-1 (TDI).
• Assessment of EHTs' functional performance (force of contraction, inotropic responses) and histological characteristics (sarcomeric organization and alignment).

Main Results:

• EHTs cultured in maturation medium (TDI) exhibited significantly higher force of contraction.
• Maturation medium improved sarcomeric organization and alignment within the EHTs.
• EHTs showed enhanced inotropic responses to isoproterenol and nifedipine when cultured in maturation medium.

Conclusions:

• The developed EHT platform provides a robust system for measuring cardiac contractility.
• Serum-free maturation medium significantly enhances the maturity and functionality of hPSC-CM derived EHTs.
• This optimized EHT platform is suitable for cardiovascular research, disease modeling, and preclinical drug testing.