Modulation of bone marrow haematopoietic stem cell activity as a therapeutic strategy after myocardial infarction: a preclinical study
Myocardial infarction (MI) is a major global health concern. Although myeloid cells are crucial for tissue repair in emergency haematopoiesis after MI, excessive myelopoiesis can exacerbate scarring and impair cardiac function. Bone marrow (BM) haematopoietic stem cells (HSCs) have the unique capability to replenish the haematopoietic system, but their role in emergency haematopoiesis after MI has not yet been established. Here we collected human sternal BM samples from over 150 cardiac surgery patients, selecting 49 with preserved cardiac function. We show that MI causes detrimental transcriptional and functional changes in human BM HSCs. Lineage tracing experiments suggest that HSCs are contributors of pro-inflammatory myeloid cells infiltrating cardiac tissue after MI. Therapeutically, enforcing HSC quiescence with the vitamin A metabolite 4-oxo-retinoic acid dampens inflammatory myelopoiesis, thereby modulating tissue remodelling and preserving long-term cardiac function after MI.
Authors
- Diana Chiang (ORCID: https://orcid.org/0000-0002-5857-1477)
- Noémie Karabacz
- Timon Bühler
- Ritika Jain (ORCID: https://orcid.org/0000-0003-4530-7578)
- Timo Heidt (ORCID: https://orcid.org/0000-0002-9607-7963)
- Peter van Galen (ORCID: https://orcid.org/0000-0002-0735-1570)
- Maria‐Eleni Lalioti (ORCID: https://orcid.org/0000-0003-3411-7832)
- Antonia Kreso (ORCID: https://orcid.org/0000-0003-0632-958X)
- Julian Mess
- Indranil Singh (ORCID: https://orcid.org/0000-0002-2143-986X)
- Katharina Schönberger (ORCID: https://orcid.org/0000-0003-4488-3688)
- Martin Czerny (ORCID: https://orcid.org/0000-0003-4766-9775)
- Achim Lother (ORCID: https://orcid.org/0000-0001-9107-5558)
- Ingo Hilgendorf (ORCID: https://orcid.org/0000-0002-0024-1643)
- Carolin Wadle
- Nadine Obier
- Nina Cabezas‐Wallscheid (ORCID: https://orcid.org/0000-0003-0870-0530)
- Yu Wei Zhang (ORCID: https://orcid.org/0000-0002-6415-694X)
- Natalie Hoppe
- Jasmin Rettkowski
- Constantin von zur Mühlen (ORCID: https://orcid.org/0000-0003-2767-8009)
- Hana Seung (ORCID: https://orcid.org/0009-0004-7754-787X)
- Alejo Rodriguez-Fraticelli (ORCID: https://orcid.org/0000-0002-4017-8714)
- Alexander Maier (ORCID: https://orcid.org/0000-0003-0200-7495)
- Mari Carmen Romero-Mulero (ORCID: https://orcid.org/0000-0002-6705-7613)
- Karin Jäcklein
- Jan Wrobel
- Claus Jülicher
- Dirk Westermann
- Marion Jones
- Mirijam Egg
- Beatriz Silva-Rego
- Helen Demollin
- Anne Hetkamp
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- University of Freiburg (DE)
- University Medical Center Freiburg (DE)
- ETH Zurich (CH)
- Massachusetts General Hospital (US)
- Institute for Research in Biomedicine (ES)
- Barcelona Institute of Science and Technology (ES)
- Max Planck Institute of Immunobiology and Epigenetics (DE)
- Universitat de Barcelona (ES)
Publication Details
- Journal
- Nature Cell Biology
- Published
- 2025-04-01
- DOI
- https://doi.org/10.1038/s41556-025-01639-4
- Citations
- 12
- Primary Topic
- Mesenchymal stem cell research
- Type
- article
- Field-Weighted Citation Impact
- 19.50