Heart patch

After 25 years of intensive basic research, the heart patch is scheduled to enter clinical testing for the first time in 2021. A story that could not be told without animal testing and scientific cooperation.

There is good news and bad news. The good: our life expectancy continues to increase with a high quality of life. The bad: Chronic heart disease, and especially heart failure, is already the number one cause of death in the world. With the currently available therapeutic measures, this situation will not change. Rather, the number of patients with heart failure will continue to increase. In 2018, more than 200,000 people died of heart failure in Germany. Wouldn't it be good to be able to repair hearts?

At the end of the 1990s, human embryonic stem cells were developed for the first time and their suitability for heart muscle tissue production was demonstrated by Zimmermann and cooperation partners in Haifa (Israel). Nevertheless, the way for clinical application in Germany remained blocked by law. Socially and politically, against the background of the ethical dilemma associated with embryonic stem cells, the approach via adult stem cells was favored. The introduction of so-called induced pluripotent stem cells from humans, bypassing embryonic stem cells, in 2007 cut the Gordian knot for Zimmermann's research in Germany as well. In 2012, the discoverer of this stem cell technology, Shinya Yamanaka, was awarded the Nobel Prize in Medicine and Physiology. At the same time, this opened the door for the heart patch approach developed by Zimmermann and colleagues to be implemented in the clinic.

Cardiac muscle cells and fibroblasts from induced pluripotent stem cells are taken up in collagen and filled into molds of almost any size to produce heart patches with a desired shape and function. To help the heart patches mature, they are mechanically stimulated and then ready for implantation after a few weeks. In 2006, Zimmermann, then freshly appointed junior professor for tissue engineering at the University Medical Center Hamburg-Eppendorf, was able to report for the first time on the successful therapeutic use of the heart plaster in rats. For this, rat heart patches were placed on the damaged heart in the rat model and then sutured.

"You can imagine this a bit like a balloon that you squeeze and it puffs out at a weak spot."

Would the development of the heart patch have been possible without animal testing? "Absolutely not," Zimmermann states. "The crucial thing before the clinical application of the heart patches is, in particular, the certainty that the patient will not be harmed. The tests required for this purpose, which are also prescribed by law, must be tested with the necessary care in a model similar to a human being. A simulation on the drawing board or experiments in the culture dish are helpful and have also been carried out extensively by us, but are not sufficient to be able to make conclusive predictions about the risk potential in humans." On the basis of the data now available, Zimmermann and his colleagues were now in a position to submit a clinical trial application to the higher federal authority, the Paul Ehrlich Institute, to carry out the world's first trial of the heart patch approach in patients. But the heart tissue manufacturing process now developed and continuously optimized by Zimmermann and colleagues also has additional benefits for applications in the laboratory: It helps reduce animal testing in other areas. "Heart preparations along the lines of our heart patch are now widely used as a replacement procedure for animal experiments in drug testing," he says.

"We've always been open about our approaches, and here we can clearly demonstrate how animal testing can contribute to the development of novel drugs."