Protocol to generate immunocompetent human heart-macrophage assembloids for the study of immune-cardiac interactions
Summary
Here, we present a protocol to generate fully human pluripotent stem cell (hPSC)-derived human heart-macrophage assembloids. We describe steps for differentiating hPSCs into monocytes, generating cardiac organoids, integrating CD14+ monocytes to become cardiac tissue-resident macrophages, and maturing the assembloids with metabolic cues. Furthermore, we provide a use-case example of disease modeling for the study of atrial arrhythmias. The system provides a reproducible, scalable, and efficient platform for studying immune-cardiac interactions, inflammation, and arrhythmogenesis. For complete details on the use and execution of this protocol, please refer to O'Hern et al.1. Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.
| Authors | O'Hern C, Dionise M, Caywood S, Sewavi ML, Basrai H, Muniyandi P, Volmert B, Kostina A, Huang A, Chalfoun N, Aguirre A |
|---|---|
| Journal | STAR protocols |
| Publication Date | 2026 Mar 20;7(1):104411 |
| PubMed | 41790550 |
| PubMed Central | PMC12992950 |
| DOI | 10.1016/j.xpro.2026.104411 |