Mechanical Conditioning: Training Engineered heart tissues

by Kate Park,

Choate Rosemary Hall, CT

Heart disease remains one of the world's leading causes of death, and heart rhythm disorders, such as arrhythmias, pose significant challenges to both patients and healthcare professionals. However, recent advances in the development of engineered heart muscle (EHM) offer hope for treating heart failure and other related conditions. One of the issues regarding lab-grown heart tissue is ensuring that it functions in sync with the heart of the patient. A recent study has uncovered a novel solution: mechanical conditioning, a process that trains lab-grown heart tissue to beat in rhythm with the patient’s heart.

EHM refers to heart tissue grown in the laboratory using stem cells. These tissues hold immense potential in treating patients with damaged heart tissue, yet one issue still remains: How can these lab-grown tissues integrate seamlessly into the cardiovascular system of the host after transplantation?

Mechanical conditioning involves applying physical forces, such as compressing and stretching, to tissue cultures. This process of applying physical force to tissue cultures has proved to be effective in influencing how the tissues behave. For instance, stretching mimics the natural movement of the heart, which is essential for ensuring functional integration into the patient’s heart.

Recently, a team of researchers subjected EHM to rhythmic, mechanical stretching for a duration of 120 hours at a frequency of 1 Hz. The goal was to see how physical stimulation affected the EHM’s beating pattern. In order to mimic the heart’s natural pumping rhythm, the researchers used a mechanical system to provide consistent stretching. Over time, the EHM adapted its beating rate and rhythm to synchronize with the stretching. This adaptation occurred without the need to connect the EHM to the host heart. In other words, mechanical forces alone were sufficient to train the heart tissue in a way that aligned with the host heart’s natural rhythm. This finding is incredibly significant because it suggests a new approach to integrating lab-grown tissue into the body without the risk of arrhythmias. Mechanically conditioned lab-grown heart tissue can provide a safer, and more efficient means of repairing damaged heart tissue. This could open new avenues of therapy other than just relying on medication and pacemakers.

Mechanosensitive ion channels are proteins that respond to mechanical forces by allowing ions to pass through the cell membrane (Haswell et al., 2011). These proteins convert mechanical stimuli to electric signals, which is crucial in signaling nerves and moving muscles. In this study, mechanosensitive ion channels likely played a pivotal role in allowing the EHM to adapt to the host heart’s natural rhythm. The mechanical, rhythmic stretching, likely activated these channels, promoting the synchronization between the the tissue’s electrical activities with the mechanical forces.

Mechanical conditioning not only helps the tissue adapt but also accelerates the maturation of the EHM. The rhythmic stretching helps align the muscle fibers in the same direction, improving overall maturity. These improvements make the tissue better suited for heart transplantation.

As researchers continue to explore mechanical conditioning, future studies may develop customized processes for different patients’ needs. These protocols could be determined by the heart rate, rhythm, and specific tissue that needs to be repaired. This would allow for more effective, personalized therapies guaranteeing that the transplanted tissue functions optimally within the patient’s unique biological environment.

Overall, this study offers a glimpse into the future of regenerative medicine, showing that mechanical conditioning can synchronize EHM with the host heart’s rhythm. The discovery could be groundbreaking for heart-rhythm disorders, offering new therapeutic strategies and improving the functionality of lab-grown tissues for transplant. As research continues to advance, these findings could lead to safer, more effective treatments for patients with heart disease requiring tissue repair.

References

Haswell, E., Phillips, R., & Rees, D. (2011). Mechanosensitive channels: What can they do and how do they do it? Structure, 19(10), 1356-1369. https://doi.org/10.1016/j.str.2011.09.005

Jebran, A.-F., Seidler, T., Tiburcy, M., Daskalaki, M., Kutschka, I., Fujita, B., Ensminger, S., Bremmer, F., Moussavi, A., Yang, H., Qin, X., Mißbach, S., Drummer, C., Baraki, H., Boretius, S., Hasenauer, C., Nette, T., Kowallick, J., Ritter, C. O., . . . Dressel, R. (2025). Engineered heart muscle allografts for heart repair in primates and humans. Nature. https://doi.org/10.1038/s41586-024-08463-0