Engineering Heart Tissue
Heart muscle does not regrow after a heart attack. Engineered cardiac tissue is being developed both as a future repair material and, already today, as a model for testing drugs.
A tissue that does not repair itself
Adult heart muscle cells, cardiomyocytes, divide very little. When a coronary artery is blocked and part of the heart wall dies, the lost muscle is replaced by scar tissue that does not contract. The heart compensates for a while, but the damage is permanent. This is the basic motivation for cardiac tissue engineering: if functional muscle could be grown outside the body, it might one day be used to patch damaged hearts.
Where the cells come from
For a long time the field was limited by the cells themselves. Adult cardiomyocytes cannot be expanded in culture, and early work relied on cells from animal hearts. The turning point was the discovery in 2006, by Shinya Yamanaka’s group, that ordinary adult cells can be reprogrammed into induced pluripotent stem cells. These cells can be turned into beating human heart cells in large numbers, and the discovery was recognised with the Nobel Prize in Physiology or Medicine in 2012.
Cells derived this way tend to resemble immature, fetal heart muscle: they are small, beat spontaneously and handle calcium differently from adult cells. A large part of current research is about maturation – finding culture conditions that make them behave more like the muscle in an adult heart.
Training tissue with electricity and load
The heart is an electrical organ. Every beat starts with an electrical impulse that spreads through the muscle, so it is natural to use electrical stimulation as a training signal. Pacing engineered tissue at physiological rates has been shown to improve the alignment of the cells, the organisation of their contractile machinery and the speed at which electrical signals travel through the construct. Mechanical stretch and gradually increasing load have similar effects, much as exercise conditions skeletal muscle.
Engineers also borrow tools from their own discipline: tissue can be cast around flexible posts whose bending reveals the force of each contraction, or grown on electrode arrays that record how the signal propagates. These measurements turn a piece of tissue into a test bench.
Tissue on a chip
The most immediate application is not implantation but testing. Many drug candidates fail late in development because of unexpected effects on heart rhythm. Small engineered heart tissues, sometimes built into microfluidic “organ-on-a-chip” devices, let researchers observe how human heart cells respond to a compound long before a clinical trial. Regulators and pharmaceutical companies have shown growing interest in such human-cell models as a complement to animal studies.
Open questions
- Building tissue thick enough to matter clinically, with its own blood supply.
- Making sure implanted cells beat in step with the host heart and do not trigger arrhythmias.
- Producing cells reproducibly, at scale, and to clinical quality standards.
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