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Developing 3D Organized Human Cardiac Tissue within a Microfluidic Platform
Published on: June 15, 2021
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Micro-Engineered Heart Tissues On-Chip with Heterotypic Cell Composition Display Self-Organization and Improved
Carla Cofiño-Fabres1, Tom Boonen2, José M Rivera-Arbeláez1,3
1Department of Applied Stem Cell Technologies, TechMed Centre, University of Twente, Enschede, 7522 NB, The Netherlands.
Advanced Healthcare Materials
|March 12, 2024
Summary
This study developed a novel Heart-on-Chip model using human cells to create miniaturized engineered heart tissues. These advanced models improve drug screening and disease modeling by mimicking heart structure and function more accurately.
Area of Science:
- Cardiovascular research
- Biomedical engineering
- Stem cell technology
Background:
- Advanced in vitro models are crucial for accurate human heart disease modeling, drug screening, and safety pharmacology.
- Conventional 3D Engineered Heart Tissues (EHTs) lack cellular complexity and flow culture, while microfluidic Heart-on-Chip (HoC) models lack 3D structure and precise contractile measurements.
- Existing models do not fully recapitulate the intricate structure and function of the human heart.
Purpose of the Study:
- To develop an innovative and user-friendly Heart-on-Chip (HoC) model that overcomes limitations of current in vitro cardiac models.
- To create self-organized miniaturized Engineered Heart Tissues (µEHTs) with enhanced physiological complexity.
- To investigate the impact of endothelial cell layers on drug responses within the µEHT model.
Main Methods:
- Culturing human pluripotent stem cell (hPSC)-derived cardiomyocytes (CMs), endothelial cells (ECs), smooth muscle cells (SMCs), and cardiac fibroblasts (FBs) within a microfluidic device.
- Utilizing flow culture conditions to promote self-organization into miniaturized Engineered Heart Tissues (µEHTs).
- Assessing contractile performance, conduction velocity, and drug responses in the developed µEHTs.
Main Results:
- The developed HoC model successfully generated self-organized µEHTs with a cardiomyocyte-endothelial cell (CM-EC) interface mimicking physiological capillaries.
- µEHTs cultured under flow exhibited enhanced contractile function and conduction velocity compared to static cultures.
- The presence of an EC layer in µEHTs modulated drug responses, suggesting a potential barrier effect influencing drug availability to cardiomyocytes.
Conclusions:
- The developed HoC model offers a more physiologically relevant platform for studying cardiac function and disease.
- These advanced cardiac µEHTs with increased complexity provide a powerful tool for predicting drug efficacy and identifying therapeutic targets.
- The findings highlight the importance of incorporating endothelial cells and flow culture for more accurate in vitro cardiac modeling.
