BRIEF RESEARCH REPORT article
Front. Cell Dev. Biol.
Sec. Embryonic Development
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1629988
This article is part of the Research TopicProceedings of Anatomy 2024 – Tripartite Meeting: The Role of Medical Embryology for Interdisciplinary ResearchView all 7 articles
Tissue-resident macrophages co-develop with myocardial tissue in human induced pluripotent stem cell-derived organoids
Provisionally accepted
- Julius Maximilian University of Würzburg, Würzburg, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The heart is the first functional organ to develop during embryogenesis, forming in parallel with the vasculature and hematopoietic cell lineages. To advance our understanding of human cardiac development and disease, human induced pluripotent stem cell (iPSC)-derived cardiomyocytes offer a promising in vitro model. However, conventional 2D cultures lack the complexity required to recapitulate the intricate interactions of different cell types leading to fully functional and mature cardiac tissue. Here, we present a human iPSC-derived 3D organoid model that develops a functional myocardium composed of cardiomyocytes and fibroblasts, capable of spontaneous rhythmic contractions. The organoid is interspersed with a branched network of endothelium-lined cavities, endothelial cords and capillary-like structures. Additionally, hemogenic endothelium co-develops with the cardiac tissue, giving rise to erythrocytes and CCR2⁻ tissue-resident macrophages that integrate into the myocardium. The model represents a complex 3D cell culture platform to study human heart tissue development with all the involved cell types (cardiomyocytes, fibroblasts, endothelial cells, macrophages), paving the way for new insights into the role of macrophages in cardiac development and disease.
Keywords: tissue resident macrophages, Erythrocytes, Hematopoiesis, induced pluripotent stem cells (iPSCs), Cardiac organoid, tissue model, Vascularisation, hemogenic endothelium
Received: 16 May 2025; Accepted: 17 Oct 2025.
Copyright: © 2025 Rockel, Brunnbauer, Wagner, Gerull, Ergün and Wörsdörfer. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Philipp Wörsdörfer, philipp.woersdoerfer@uni-wuerzburg.de
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.