German scientists have created lab-grown “patches” of heart muscle tissue derived from pluripotent stem cells. Following a success with rhesus monkeys, they have obtained approval for a human trial [1].
Wear and tear
As one of the most hard-working tissues in the body, the heart muscle is subject to incessant wear and tear due to aging and various health conditions. Unsurprisingly, heart failure is one of the most common age-related causes of death.
Scientists have tried to repair damaged heart tissue by injecting healthy heart muscle cells (cardiomyocytes), but retention and rejection issues are abundant. In a new study published in Nature, a group of German researchers has reported on an exciting new technique: growing entire patches of brand-new heart tissue from scratch.
Let it grow
The process starts with induced pluripotent stem cells (iPSCs), which are cells that were de-differentiated using cellular reprogramming methods into a stem-like pluripotent state. Such cells can then be re-differentiated into many cell types. Reprogramming also makes them epigenetically younger, so they are ready to do heavy lifting.
These newly differentiated cardiomyocytes are then mixed with stromal cells that provide structural support, and a patch of something closely resembling heart muscle tissue is grown in culture. The researchers call these structures engineered heart muscle (EHM).
After a series of previous experiments in rodent models, the group decided to take a major step up and move to non-human primates. While it is possible to produce iPSCs from the patient’s own cells, the researchers decided to use existing lines of iPSC-derived cardiomyocytes. The trade-off was the need for immunosuppression.
A group of rhesus macaques was subjected to a procedure imitating heart failure, and then their injured hearts were reinforced with EHMs in two different doses: either two or five patches. The higher dose uses about 200 million cardiomyocytes.
High retention, improved function
With both doses, but more so with the higher one, the researchers achieved a sustained and significant increase in heart wall thickness. Two of the three monkeys in the high dose group also showed increased heart wall contractility, indicating improved heart function.
The engrafted tissue, which initially lacked its own blood vessels, underwent vascularization upon implantation, even though blood perfusion was not as good as in the surrounding tissue. EHM cardiomyocytes were less developed, “younger,” than their resident counterparts, which is to be expected. It remains to be seen to what degree they can eventually develop.
Importantly, graft retention was confirmed for up to six months after the procedure, when the study ended. The researchers claim that this is the best result achieved by anyone so far.
Now, to humans!
In another experiment, the group previously implanted EHMs in a human patient who was awaiting a transplant for his severely damaged heart. After the new heart was transplanted, the researchers were able to study how their EHM patches performed on the old one.
Just like in monkeys, cardiomyocyte retention was good, and a high degree of vascularization was achieved. The patient demonstrated a stable disease course. “Collectively, the obtained clinical data confirmed the translatability of heart remuscularization by EHM allograft implantation from rhesus macaques to human patients with advanced heart failure,” the paper says.
“We have shown in rhesus macaques that cardiac patch implantation can be applied to re-muscularize the failing heart. The challenge was to generate and implant enough heart muscle cells from rhesus macaque induced pluripotent stem cells to achieve sustainable heart repair without dangerous side effects such as cardiac arrhythmia or tumor growth,” said Professor Wolfram-Hubertus Zimmermann, director of the Department of Pharmacology and Toxicology at the University Medical Center Göttingen, the study’s lead author.
Based on these results, the researchers have secured approval for a first-of-its-kind trial in human patients: “Safety and Efficacy of Induced Pluripotent Stem Cell-derived Engineered Human Myocardium as Biological Ventricular Assist Tissue in Terminal Heart Failure.”
Literature
[1] Jebran, AF., Seidler, T., Tiburcy, M. et al. (2025). Engineered heart muscle allografts for heart repair in primates and humans. Nature.
