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Human iPSC-cardiomyocyte-aggregate cell therapy in non-human primates and correlation of heart recovery with contractile and electrophysiological cardiomyocyte properties.

Overview

Authors: Ina Gruh1,2,3, Andreas Martens1,2,3, Serghei Cebotari1,2,4, Annette Schrod5, Alexandra Haase1,2, Caroline Halloin1,2, Wiebke Triebert1,2, Nils Kriedemann1,2, Tobias Goecke1,2,6, Morsi Arar2,3, Klaus Hoeffler2, Paul Frank7, Karen Lampe5, Amir Moussavi5, Anna Kuleshova1,2, Vojtech Hradil1,2, Veronika Fricke1,2, Monika Szepes1,2, Kerstin Mätz-Rensing5, Jörg Eiringhaus7
and 23 other authorsAnna-Lena de Vries7, Stephan Hohmann7, Merlin Witte1,2, Tim Kohrn1,2, Jana Teske1,2, Kevin Cyrys1,2, Sara Szadocka1,2, Annika Franke1,2, Christopher Werlein8, Karlo Komorowski9, Mark Kühnel10, Danny Jonigk10, Susann Boretius5, Christian Veltmann7, David Duncker7, Jonathan Jung11, Nissim Benvenisty11, Jeanne de la Roche12, Martin Fischer12, Axel Haverich1,2, Arjang Ruhparwar2,6, Robert Zweigerdt1,2, Ulrich Martin1,2,6
ORCID iDs: Alexandra Haase, Nils Kriedemann, Stephan Hohmann, Kevin Cyrys, Christopher Werlein, Karlo Komorowski, Danny Jonigk, Susann Boretius, David Duncker, Nissim Benvenisty, Jeanne de la Roche, Martin Fischer, Robert Zweigerdt, Ulrich Martin
  1. Leibniz Research Laboratories for Biotechnology and Artificial Organs, Cluster of Excellence REBIRTH, Carl-Neuberg-Straße 1, Hannover Medical School,Hannover, Germany
  2. Dept. of Cardiac, Thoracic, Transplantation and Vascular Surgery, Cluster of Excellence REBIRTH, Hannover Medical School,Hannover, Germany
  3. Dept. of Cardiac Surgery, Carl von Ossietzky University Oldenburg,Oldenburg, Germany
  4. Dept. of Cardiac Surgery, Institute for Cardiac Surgery and Interventional Cardiology, INCCI Heart-Center Foundation, Luxembourg, Luxembourg
  5. German Primate Center, Leibniz Institute for Primate Research,Göttingen, Germany
  6. Biomedical Research in Endstage and Obstructive Lung Disease (BREATH), German Center for Lung Research (DZL), Hannover Medical School,Hannover, Germany
  7. Hannover Heart Rhythm Center, Department of Cardiology and Angiology, Hannover Medical School,Hannover, Germany
  8. Department of Pathology, Hannover Medical School,Hannover, Germany
  9. Department of Radiation Protection and Medical Physics, Hannover Medical School,Hannover, Germany
  10. Institute of Pathology, University Hospital RWTH Aachen,Aachen, Germany
  11. Department of Genetics, The Hebrew University of Jerusalem,Jerusalem, Israel
  12. Institute of Neurophysiology, Hannover Medical School,Hannover, Germany
Institutions: Medizinische Hochschule Hannover (Germany); Carl von Ossietzky Universität Oldenburg (Germany); German Primate Center (Germany); RWTH Aachen University (Germany); Hebrew University of Jerusalem (Israel)
Journal: Nature communications, volume 17, issue 1, article 9066
Dates: received 10 April 2025; accepted 13 August 2026; published online 26 August 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-77103-0 · PMID 42649227 · PMCID PMC13518835 · OpenAlex W7204246334
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: human (organism), non-human primate (organism), cellular / molecular (subfield)
Methods: Statistics
Keywords: Stem-cell research, Induced pluripotent stem cells, Heart stem cells, Cardiology
MeSH: Cell- and Tissue-Based Therapy*, Induced Pluripotent Stem Cells*, Myocardial Infarction*, Myocytes, Cardiac*, Animals, Arrhythmias, Cardiac, Cell Differentiation, Electrophysiological Phenomena, Heart, Humans, Macaca fascicularis, Myocardial Contraction (* major topic)
Topic: Pluripotent Stem Cells Research (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: Deutsche Forschungsgemeinschaft (DFG) (REBIRTH EXC 62/2, ZW64/4-2, KFO311 / ZW64/7-1, JO743/4-1); Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) (01EK1601A, 13XP5092B, 031L0249, 01EK2108A, German Center for Lung Research (DZL, 82DZL002C1)); Niedersächsische Ministerium für Wissenschaft und Kultur (Lower Saxony Ministry of Science and Culture) (ZN3340); EC | Horizon 2020 Framework Programme (EU Framework Programme for Research and Innovation H2020) (101056712)
Citations: not cited yet (Europe PMC); 57 references in the paper

Abstract

This study demonstrates the successful production and injection of human induced pluripotent stem cell cardiomyocyte aggregates into infarcted cynomolgus monkey hearts, resulting in substantial, structured human grafts three months after cell transplantation. Transient graft-induced arrhythmias decreased over time. Both the arrhythmogenicity and the substantial heart function recovery in vivo notably seemed to correlate with induced pluripotent stem cell clone-dependent contractile and electrophysiological cardiomyocyte properties in vitro. Overexpression of a red fluorescent reporter protein led to a dysregulated conduction and contraction machinery in yet engraftment competent cardiomyocytes, providing an important tool to mechanistically understand and improve induced pluripotent stem cell-based heart repair in preclinical models.

We demonstrate the logistically important, temporal uncoupling of cardiomyocyte production from transplantation. Cardiomyocyte aggregate transplantation yielded results comparable to the reported transplantation of 10-20-fold higher numbers of dissociated human embryonic stem cell- cardiomyocytes and suggests a higher degree of cell/ tissue maturation in cardiac grafts. Our study promotes reduced cell production costs, highlights the need for an in vitro potency assay, and shows a pragmatic new avenue for the clinical translation of human induced pluripotent stem cell-based heart repair.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none, so it has no map.

Data

Datasets cited

Data availability

The authors declare that all data supporting the findings of this study are available within the article and its Supplementary Information files, or in the source data provided with this paper. RNASeq data have been deposited in the NCBI Sequence Read Archive (SRA) under the BioProject ID PRJNA1248569. (https://www.ncbi.nlm.nih.gov/bioproject/?term=PRJNA1248569).

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 43 authors, 4 keywords, 12 MeSH terms, 4 funders, 57 references.

Cite

This paper

Gruh, I., Martens, A., Cebotari, S., Schrod, A., Haase, A., Halloin, C., Triebert, W., Kriedemann, N., Goecke, T., Arar, M., Hoeffler, K., Frank, P., Lampe, K., Moussavi, A., Kuleshova, A., Hradil, V., Fricke, V., Szepes, M., Mätz-Rensing, K., . . . Martin, U. (2026). Human iPSC-cardiomyocyte-aggregate cell therapy in non-human primates and correlation of heart recovery with contractile and electrophysiological cardiomyocyte properties. Nature communications, 17(1), 9066. https://doi.org/10.1038/s41467-026-77103-0

BibTeX

@article{gruh2026human,
author = {Gruh, Ina and Martens, Andreas and Cebotari, Serghei and Schrod, Annette and Haase, Alexandra and Halloin, Caroline and Triebert, Wiebke and Kriedemann, Nils and Goecke, Tobias and Arar, Morsi and Hoeffler, Klaus and Frank, Paul and Lampe, Karen and Moussavi, Amir and Kuleshova, Anna and Hradil, Vojtech and Fricke, Veronika and Szepes, Monika and Mätz-Rensing, Kerstin and Eiringhaus, Jörg and de Vries, Anna-Lena and Hohmann, Stephan and Witte, Merlin and Kohrn, Tim and Teske, Jana and Cyrys, Kevin and Szadocka, Sara and Franke, Annika and Werlein, Christopher and Komorowski, Karlo and Kühnel, Mark and Jonigk, Danny and Boretius, Susann and Veltmann, Christian and Duncker, David and Jung, Jonathan and Benvenisty, Nissim and de la Roche, Jeanne and Fischer, Martin and Haverich, Axel and Ruhparwar, Arjang and Zweigerdt, Robert and Martin, Ulrich},
title = {{Human iPSC-cardiomyocyte-aggregate cell therapy in non-human primates and correlation of heart recovery with contractile and electrophysiological cardiomyocyte properties}},
journal = {Nature communications},
year = {2026},
month = aug,
volume = {17},
number = {1},
pages = {9066},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-77103-0},
url = {https://doi.org/10.1038/s41467-026-77103-0},
pmid = {42649227},
pmcid = {PMC13518835}
}

RIS

TY - JOUR
AU - Gruh, Ina
AU - Martens, Andreas
AU - Cebotari, Serghei
AU - Schrod, Annette
AU - Haase, Alexandra
AU - Halloin, Caroline
AU - Triebert, Wiebke
AU - Kriedemann, Nils
AU - Goecke, Tobias
AU - Arar, Morsi
AU - Hoeffler, Klaus
AU - Frank, Paul
AU - Lampe, Karen
AU - Moussavi, Amir
AU - Kuleshova, Anna
AU - Hradil, Vojtech
AU - Fricke, Veronika
AU - Szepes, Monika
AU - Mätz-Rensing, Kerstin
AU - Eiringhaus, Jörg
AU - de Vries, Anna-Lena
AU - Hohmann, Stephan
AU - Witte, Merlin
AU - Kohrn, Tim
AU - Teske, Jana
AU - Cyrys, Kevin
AU - Szadocka, Sara
AU - Franke, Annika
AU - Werlein, Christopher
AU - Komorowski, Karlo
AU - Kühnel, Mark
AU - Jonigk, Danny
AU - Boretius, Susann
AU - Veltmann, Christian
AU - Duncker, David
AU - Jung, Jonathan
AU - Benvenisty, Nissim
AU - de la Roche, Jeanne
AU - Fischer, Martin
AU - Haverich, Axel
AU - Ruhparwar, Arjang
AU - Zweigerdt, Robert
AU - Martin, Ulrich
TI - Human iPSC-cardiomyocyte-aggregate cell therapy in non-human primates and correlation of heart recovery with contractile and electrophysiological cardiomyocyte properties
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/08/26
VL - 17
IS - 1
SP - 9066
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-77103-0
UR - https://doi.org/10.1038/s41467-026-77103-0
LA - en
ER -

CSL-JSON

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}

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