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A living patch for damaged hearts

A new artificially grown human heart muscle that acts just like natural tissue could be important in treating heart attack patients or in serving as a platform for testing new heart disease medicines, according to a study1 published recently in Biomaterials.

The “heart patch” developed by biomedical engineers at Duke University (Durham, North Carolina, USA), using pluripotent human embryonic stem cells, conducts electricity at roughly the same speed as natural heart cells, and ‘squeezes’ appropriately. Earlier attempts to create functional heart patches have largely been unable to overcome those obstacles, say the authors.

“The structural and functional properties of these 3-D tissue patches surpass all previous reports for engineered human heart muscle,” said Dr Nenad Bursac, associate professor of biomedical engineering at Duke’s Pratt School of Engineering. “This is the closest man-made approximation of native human heart tissue to date.”

“In past studies, human stem cell-derived cardiomyocytes were not able to both rapidly conduct electrical activity and strongly contract as well as normal cardiomyocytes,” Dr Bursac said. “Through optimisation of a three-dimensional environment for cell growth, we were able to ‘push’ cardiomyocytes to reach unprecedented levels of electrical and mechanical maturation.”

Fwd_ Duke News -- Duke Scientists Build a Living Patch for Damaged Hearts

Dr Nenad Bursac (Duke University, North Carolina, USA)

The rate of functional maturation is an important element for the patch to become practical, said Dr Bursca – while it takes about nine months for a neonatal functioning heart to develop in a developing human embryo, advancing the functional properties of these bioengineered patches took little more than a month. “Currently, it would take us about five to six weeks starting from pluripotent stem cells to grow a highly functional heart patch,” he said, adding that as technology advances, the time should shorten.

“When someone has a heart attack, a portion of the heart muscle dies,” Dr Bursac said. “Our goal would be to implant a patch of new and functional heart tissue at the site of the injury as rapidly after heart attack as possible. Using a patient’s own cells to generate pluripotent stem cells would add further advantage in that there would likely be no immune system reaction, since the cells in the patch would be recognised by the body as self.”

In addition to a possible therapy for patients with heart disease, Dr Bursac said that engineered heart tissues could also be used to effectively screen new drugs or therapies: “Tests or trials of new drugs can be expensive and time-consuming. Instead of, or along with testing drugs on animals, the ability to test on actual, functioning human tissue may be more predictive of the drugs’ effects and help determine which drugs should go on to further studies.”

The current experiments were conducted on one human pluripotent stem cell line. Dr Bursac and his colleagues have reproduced their findings on two other cell lines and are testing additional lines. They are also planning to move to larger animal models to learn how the patch would become functionally integrated with its host and how the patch establishes connections with the circulatory system.

Speaking to BJC Arrhythmia Watch, Dr Bursac said: “In terms of adopting this technology to routine clinical practice, I would anticipate that it will take another 10 years of careful tests before this approach would reach clinics. At the current stage, the technology can be utilised for drug development and toxicology studies, but getting to clinical practice will require careful demonstration of safety and efficacy in large animal models.”

“The hope is that potential functional benefits of such a tissue engineering approach will offset risks that open heart surgery (currently the only mode of patch delivery) may incur. A stepping stone in this process will be the use of pluripotent stem cell-derived cardiomyocytes (as cell injections rather than a patch) in clinical trials, which is something that I could envision happen in the next five years,” he added.

References

1. Zhang D, Shadrin IY, Lamb J, Xian HQ, Snodgrass HR, Bursac N. Tissue-engineered cardiac patch for advanced functional maturation of human ESC-derived cardiomyocytes. Biomaterials 2013;34:5813–20. http://dx.doi.org/10.1016/j.biomaterials.2013.04.026

Published on: May 22, 2013

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