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Developing 3D Organized Human Cardiac Tissue within a Microfluidic Platform
Published on: June 15, 2021
Variable optimization for the formation of three-dimensional self-organized heart muscle
Luda Khait1, Chani J Hodonsky, Ravi K Birla
1Division of Cardiac Surgery, Artificial Heart Laboratory, Ann Arbor, MI 48103, USA.
In Vitro Cellular & Developmental Biology. Animal
|September 17, 2009
Summary
This study characterizes cardioids, a novel 3D heart muscle model, demonstrating gene expression similar to native heart tissue. Optimization revealed specific culture conditions enhance cardioid function for tissue engineering applications.
Area of Science:
- Biomedical Engineering
- Cardiovascular Research
- Regenerative Medicine
Background:
- Cardiac tissue engineering aims to create functional 3D heart muscle in vitro for studying organogenesis and disease.
- Cardioids, a scaffold-free 3D heart muscle model, have previously shown functional contractility and electrical pacing capabilities.
- Previous work established cardioids generate significant twitch and specific forces, pacing up to 10 Hz without fatigue.
Purpose of the Study:
- To further characterize the cardioid model by analyzing its gene expression profile.
- To optimize cardioid formation and function by evaluating key cell culture variables.
- To validate the cardioid model as a representative in vitro system for cardiac research.
Main Methods:
- Gene expression analysis of cardioids compared to 2D cultures and native heart muscle.
- Systematic variation of cell plating density, adhesion protein concentration (laminin, fibronectin), myocyte purity, and ascorbic acid levels.
- Assessment of cardioid function using twitch force in response to electrical stimulation as the primary endpoint.
Main Results:
- Cardioids exhibit gene expression patterns comparable to native mammalian heart muscle, with significantly higher expression of key cardiac genes (e.g., alpha-MHC, beta-MHC, SERCA2, phospholamban) than 2D cultures.
- Optimal plating density for maximum twitch force was identified as 3-4 x 10^6 cells per cardioid.
- Increased adhesion protein concentration and myocyte purity decreased twitch force, while ascorbic acid increased baseline force.
Conclusions:
- Cardioids present a valid in vitro model of 3D heart muscle with gene expression mirroring native tissue.
- Specific cell culture parameters, including plating density and ascorbic acid supplementation, can be modulated to enhance cardioid formation and contractile function.
- These findings provide valuable insights for optimizing cardiac tissue engineering models and may be transferable to other tissue engineering applications.
