Animal studies confirm the safety and effectiveness of the heart patch

Results from rhesus macaques provide solid ground for a first-in-human investigation of heart repair with stem cell-derived engineered heart muscle. The study is a milestone for the clinical application of the 'heart patch' as an innovative treatment option for patients with advanced heart failure.

This is how the heart patch works

Implantation of a tissue engineered heart patch, called engineered heart muscle (EHM), is developed to repair the failing heart. The EHM patch is a lab-grown heart muscle made up of induced pluripotent stem cell-derived heart cells embedded in a collagen hydrogel.

First patients successfully treated

An interdisciplinary team led by Professor Wolfram-Hubertus Zimmermann, director of the Department of Pharmacology and Toxicology at the University Medical Center (UMG) and Scientific Director of the preclinical and clinical heart patch studies, together with colleagues from the UMG and UKSH, has successfully implanted the so-called "heart patch" in patients with heart failure for the first time.

Studies on rhesus monkeys decisive

The approval of this clinical trial by the responsible regulatory authority, the Paul-Ehrlich-Institute, was preceded by the documentation of safety and efficacy of the heart patch in rhesus macaques. The simulation of the clinical application in rhesus macaques at the German Primate Center - Leibniz Institute for Primate Research (DPZ) was essential to gather compelling data to support clinical translation. The researchers were able to show that implanted heart patches, consisting of up to 200 million cells, led to an improvement in heart function through re-muscularization (building of new heart muscle). Imaging techniques and tissue analysis confirmed that the implanted heart muscle cells are retained under concomitant immune suppression and strengthened the heart's pumping function.

“We have shown in rhesus macaques that cardiac patch implantation can be applied to re-muscularized 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,” explains Professor Zimmermann. The results of the now reported investigations were crucial for the approval of the world's first clinical trial to repair the heart with tissue engineered heart muscle implants developed in the laboratory in people with advanced heart failure.

“The preclinical study in rhesus monkeys recommended and supervised by the Paul-Ehrlich-Institut shows the importance of primate research in testing novel therapies before they can be used in patients.”

Prof. Dr. Rüdiger Behr, Head of the Stem Cell and Regeneration Biology Research Platform at the DPZ

Preclinical testing of the heart patch treatment has been completed in collaboration with the DPZ and Stanford University. Based on these results, the BioVAT-HF-DZHK20 clinical trial was initiated at the UMG and UKSH in cooperation with the German Centre for Cardiovascular Research (DZHK) and Repairon GmbH in Göttingen.

Portrait of Prof. Dr. Wolfram-Hubertus Zimmermann, Director of the Institute of Pharmacology and Toxicology at the University Medical Center Göttingen. He is wearing a dark blue shirt and looking directly at the camera. The background is bright and blurred.

“Our work demonstrates for the first time that myocardial repair through re-muscularization is possible in humans. Bench to bed translation was a true tour-de-force made possible by collaborative, interdisciplinary efforts over many years.”

Professor Wolfram-Hubertus Zimmermann, Director of the Department of Pharmacology and Toxicology at the University Medical Center Göttingen (UMG)

Background Heart Patch

The heart patch technology was developed by Zimmermann and colleagues over a period of more than 30 years, from its inception to clinical application. The late preclinical preparation of the BioVAT-HF-DZHK20 clinical trial (2014-2021) was informed by scientific advice obtained from the responsible regulatory authority, the Paul Ehrlich Institute. Since 2021, patients with advanced heart failure despite optimal medical therapy are treated at the UMG and the UKSH, Campus Lübeck. The German Center for Cardiovascular Research (DZHK) and Repairon GmbH, a spin-off of the UMG, supported both the preclinical and clinical studies. Following simulations in rhesus macaques under ‘clinical conditions’ at the DPZ, a total of 15 patients have already been treated with ten billion cardiac muscle cells from induced pluripotent stem cells delivery as engineered heart muscle (EHM). Following dose optimization, the interim data on the clinical use of heart patches made from 800 million heart muscle cells in patients with severe heart failure are expected by the end of 2025.

Original Publication

Jebran AF, Seidler T, Tiburcy M, Daskalaki M, Kutschka I, Fujita B, Ensminger S, Bremmer F, Moussavi A, Yang H, Qin X, Mißbach S, Drummer C, Baraki H, Boretius S, Hasenauer C, Nette T, Kowallick J, Ritter CO, Lotz J, Didié M, Mietsch M, Meyer T, Kensah G, Krüger D, Sakib MS, Kaurani L, Fischer A, Dressel R, Rodriguez-Polo I, Stauske M, Diecke S, Maetz-Rensing K, Gruber-Dujardin E, Bleyer M, Petersen B, Roos C, Zhang L, Walter L, Kaulfuß S, Yigit G, Wollnik B, Levent E, Roshani B, Stahl-Henning C, Ströbel P, Legler T, Riggert J, Hellenkamp K, Voigt JU, Hasenfuß G, Hinkel R, Wu JC, Behr R & Zimmermann WH. Engineered heart muscle allografts for heart repair in primates and humans. Nature (2025).
DOI: 10.1038/s41586-024-08463-0