Year after year, heart disease maintains its consistent status as the world's leading cause of death, with its mortality rate in the U.S. equaling one death every 36 seconds. But to alleviate its burden, researchers are steadily working toward a future with human engineered heart tissue patches that can heal hearts harmed by the condition.

Almost all types of heart disease stem from, or lead to, injury to the heart itself. This results in loss of cardiac muscle cells, or cardiomyocytes. In a paper published March 2 in Circulation, German researchers add a new development that takes their prototype of transplantable human engineered heart patches, which they say can regenerate cardiac cells, one step closer to the clinic. 

Although negative heart disease outcomes have been reduced over time, in the year 2019 alone, 8.9 million people died globally because of the ailment, accounting for 16% of deaths worldwide. 

"Current pharmacotherapy has improved life expectancy for heart failure patients," Florian Weinberger, one of the paper's lead authors, told The Academic Times. "Yet, it does not address the underlying cause, which often is the loss of cardiomyocytes."

He added, "We think that the transplantation of engineered cardiac constructs has the potential to repair the injured heart and thereby provide a new therapeutic option."

Weinberger, a physician and professor at University Medical Center Hamburg-Eppendorf, is one of many researchers working on a method for engineered heart tissue transplants.

"We, and other groups, have been working on this strategy for many years," he said. "It has been pioneered by the head of our department, Thomas Eschenhagen, 25 years ago." 

Although associated studies have been successful, heart patches have only been transplanted into animals so far. But recently, Weinberger's team reached a milestone by characterizing specific attributes that the patches will need in order to be an option for humans. 

Remuscularization of the heart is dose-dependent, and Weinberger emphasized that, "The approach requires a large number of human myocytes." 

Additionally, cardiomyocyte proliferation, or rapid division of cells, is highly important. The researchers also discovered the ideal dimensions that the patch would need in order to be placed onto a human heart. The human-scale patches they designed were 5 cm by 7 cm, but Weinberger noted that the size will ultimately depend on the region of the heart that requires the patch; the cell number added should be equal to what is required on the muscle.

"We describe the generation of a human-scale patch — size and cell number — that was stable enough to allow a transplantation in a large animal, whereas smaller patches did not withstand the force of a larger heart," he said.

In this proof-of-principle study, the patches composed of human heart muscle cells were placed onto the hearts of guinea pigs, as these animals have a heart that is relatively big enough to provide a starting point for putting these patches in larger hearts and they can sustain human cells. More specifically, the patches are comprised of human pluripotent stem cells.

Pluripotent stem cells are the "kings" of stem cells, because they can create virtually any type of cell or tissue in the body. They can also self-renew, meaning they meet the criteria of high cardiomyocyte proliferation that Weinberger's team coined as vital for the patch's success in humans. 

"Pluripotent stem cells are the only source for human cardiomyocytes," he said. "We hypothesize that the new myocytes actively participate in the force-development of the heart."

Although researchers have yet to study how the cardiomyocytes will contribute to the muscle's strength of force, the team's findings from the guinea pig hearts show promise that it will actually add to it. 

The next step toward the clinic is the successful implementation of these patches in pigs, whose hearts are so similar to those of humans that they are discussed as having the potential to be fully transplanted into a patient. After that, the researchers believe it can be tested on humans.

"We plan to start a clinical trial within three to five years," he said, adding that some other groups have already started clinical trials that include stem cell-derived cardiomyocytes. At the very least, Weinberger hopes he can improve the approach for anyone attempting to place these patches into humans.

One hurdle that needs to be crossed is the inevitable need for immune suppression before a patient receives the patch, a common risk with foreign stem cell transplants. However, the research team has plans to avoid this issue.

"We entered a partnership with Evotec AG to develop hypoimmunogenic heart muscle patches that will spare patients from long-term high dose immune suppression therapy," Weinberger said.

The study, "Human Engineered Heart Tissue Patches Remuscularize the Injured Heart in a Dose-Dependent Manner," published March 2 in Circulation, was authored by Eva Querdel, Deniz Köse, Birgit Geertz, Marina Reinsch, Svenja Reich, Jascha Sani, Bärbel Ulmer, Mirja Schulze, Tobias Krause, Marta Lemme, Constantin v. Bibra, Aya Shibamiya, Tim Stüdemann, Yusuf Nejahsie, Arne Hansen, Ingra Mannhardt, Torsten Christ, Thomas Eschenhagen, Florian Weinberger, University Medical Center Hamburg-Eppendorf; Liesa Castro, Marc D. Lemoine, Maria Köhne, Simon Pecha, Hermann Reichenspurner, German Centre for Cardiovascular Research; Andrea Bähr, Nadja Hornaschewitz, Nikolai Klymiuk, C. Kupatt, I. Medizinische Klinik & Poliklinik, University Clinic Rechts der Isar; and M. Krane, German Heart Centre Munich.