A Living Patch for Damaged Hearts

Duke University scientists have constructed a three-dimensional human heart muscle patch that behaves much like natural heart muscle tissue. This advance could be used to either treat heart attack patients or to test new heart medicines.

This “heart patch” was grown in the laboratory from human cells, and the procedures used in this research overcame two large roadblocks. First the patch conducts electrochemical impulses at the same speed as normal adult human heart tissue and it contracts to the same degree as normal human heart tissue. In the past, heart tissue patches have conducted electrochemical impulses too slowly and contracted weakly.

The cell source used by the Duke University team were human embryonic stem cells. Thus, the heart patch would not be appropriate for human patients, since it would be rejected by the patient’s immune system. However, the procedures used in this research could also be applied to heart muscle cells made from induced pluripotent stem cells.

Nenad Bursac, associate professor of biomedical engineering at Pratt Engineering, said, “The structural and functional properties of these 3-D tissue patches surpass all previous reports for engineered human heart muscle. This is the closest man-made approximately of native human heart tissue to date.” Bursac also said that the approach does not involve genetic manipulation of the cells.

Bursac continued: “In past studies, human stem cell-derived cardiomyocytes (that is, heart muscle cells) were not able to both rapidly conduct electrical activity and strongly contract as well as normal cardiomyocytes. Through optimization of a three-dimensional environment for cell growth, we were able to ‘push’ cardiomyocytes to reach unprecedented levels of electrical and mechanical maturation.”

The rate of functional maturation is a procedural issue that has very practical implications. If clinicians want to make a heart patch for a patient, the time required to make the heart patch is important, since a heart patch that takes too long to make is of no clinical use to heart patients. In the developing human, it takes about nine months for the newborn heart to develop and an additional five years to reach adult levels of function. These heart patches, however, were grown in about 1 month. And, according to Brusac, further work should shorten the time required to make such a heart patch.

Bursac commented: “It would take us about five to six weeks starting from pluripotent stem cells to grow a highly functional heart patch. When someone has a heart attack, a portion of the heart muscle dies. 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 recognized by the body as self.”

Bursac added that besides using these heart patches in patients, the patches could also be used in the laboratory to test new heart medicines and to model heart pathologies.

“Tests of 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 into further studies.”

Some drug tests are conducted on two-dimensional sheets of heart cells, but according to Bursac, the three-dimensional culture of heart muscle cells provides a more realistic model system for drug testing.  Engineered heart tissues from patients who suffer from cardiac diseases could be used as a model to study that disease and test and explore potential therapies.

Even though Bursac used a particular embryonic stem cell line, but his co-workers also were able to replicate these results with two other embryonic stem cell lines.  Bursac also wants to test his heart muscle patches in animals to determine how well they integrate into the host heart tissue and how well they conduct electrical signals.