Developing 3D Organized Human Cardiac Tissue within a Microfluidic Platform.

Area of Science:

• Biomedical Engineering
• Cardiovascular Research
• Stem Cell Biology

Background:

• Cardiovascular disease (CVD) remains a leading global cause of death.
• In vitro modeling of the human myocardium is challenging due to limitations in obtaining adult or adult-like cardiomyocytes.
• Human induced pluripotent stem cells (hiPSCs) offer a promising source for generating human cardiomyocytes (hiPSC-CMs) for cardiac tissue engineering.

Purpose of the Study:

• To develop a protocol for creating a 3D mature, stem cell-derived human cardiac tissue model.
• To engineer an in vitro anisotropic cardiac tissue-on-a-chip using hiPSC-CMs that mimics native myocardial architecture.
• To establish a platform for fundamental cardiac biology studies, disease modeling, and pharmaceutical screening.

Main Methods:

• Developed a purification protocol to isolate hiPSC-derived cardiomyocytes (hiPSC-CMs).
• Co-cultured hiPSC-CMs with human cardiac fibroblasts (hCFs) in a defined ratio within a collagen-based hydrogel.
• Utilized a microfluidic device with staggered elliptical microposts to induce cellular and matrix alignment, creating anisotropic cardiac tissue.

Main Results:

• Successfully produced a 3D anisotropic cardiac tissue-on-a-chip model from hiPSC-CMs.
• Demonstrated the ability of microfluidic surface topography to guide cell and hydrogel alignment, mimicking native myocardium.
• Established a reproducible protocol for generating complex cardiac tissue constructs.

Conclusions:

• The developed 3D anisotropic cardiac tissue-on-a-chip model provides a more physiologically relevant in vitro system.
• This model addresses limitations in current cardiac tissue engineering by utilizing hiPSC-CMs and microfluidic technology.
• The platform holds significant potential for advancing cardiovascular research, disease modeling, and drug discovery.