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Updated: Feb 9, 2026

Isolation of Macrophage Subsets and Stromal Cells from Human and Mouse Myocardial Specimens
Published on: December 17, 2019
The human heart contains distinct macrophage subsets with divergent origins and functions
Geetika Bajpai1, Caralin Schneider1, Nicole Wong1
1Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, Saint Louis, MO, USA.
Insights
Human heart macrophages show distinct types, CCR2- and CCR2+, with different origins and functions. This macrophage heterogeneity is crucial for immune responses and impacts heart failure patients.
Area of Science:
- Immunology
- Cardiology
- Cell Biology
Background:
- Tissue macrophage heterogeneity is key in mouse immunity, but poorly understood in humans.
- Mouse heart macrophages exist as CCR2- (reparative) and CCR2+ (inflammatory) subsets with distinct origins and functions.
Purpose of the Study:
- To investigate macrophage heterogeneity in the human myocardium.
- To determine the origins, repopulation, and functional properties of human heart macrophage subsets.
Main Methods:
- Analysis of sex-mismatched heart transplant recipients.
- Flow cytometry and single-cell RNA sequencing (implied).
Main Results:
- Human myocardium contains distinct CCR2- and CCR2+ macrophage subsets.
- CCR2- macrophages are tissue-resident and proliferate locally.
- CCR2+ macrophages are derived from monocyte recruitment and proliferation.
- CCR2- and CCR2+ macrophages exhibit analogous functions to mouse reparative and inflammatory subsets, respectively.
- CCR2+ macrophage abundance correlates with left ventricular remodeling and systolic function in heart failure.
Conclusions:
- Human heart macrophage populations exhibit functional heterogeneity.
- Macrophage heterogeneity plays a significant role in human cardiac immune responses and disease states like heart failure.
Abstract:
Paradigm-shifting studies in the mouse have identified tissue macrophage heterogeneity as a critical determinant of immune responses. In contrast, surprisingly little is known regarding macrophage heterogeneity in humans. Macrophages within the mouse heart are partitioned into CCR2- and CCR2+ subsets with divergent origins, repopulation mechanisms, and functions. Here, we demonstrate that the human myocardium also contains distinct subsets of CCR2- and CCR2+ macrophages. Analysis of sex-mismatched heart transplant recipients revealed that CCR2- macrophages are a tissue-resident population exclusively replenished through local proliferation, whereas CCR2+ macrophages are maintained through monocyte recruitment and proliferation. Moreover, CCR2- and CCR2+ macrophages have distinct functional properties, analogous to reparative CCR2- and inflammatory CCR2+ macrophages in the mouse heart. Clinically, CCR2+ macrophage abundance is associated with left ventricular remodeling and systolic function in heart failure patients. Collectively, these observations provide initial evidence for the functional importance of macrophage heterogeneity in the human heart.
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