Macrophage engineering and human microtissues

Our research group at University Health Network in Toronto combines macrophage biology, human cardiac tissue engineering and mouse genetics to investigate how immune cells support tissue function and how these properties can be directed towards repair. We are seeking partners developing proposals for the 2027 Horizon Europe Cluster 1 calls.

A central strength is integrating human stem cell-derived macrophages into engineered cardiac microtissues containing cardiomyocytes and fibroblasts. In our 2024 Nature Cardiovascular Research study, macrophages promoted cardiomyocyte maturation, increased contractile force and improved relaxation through efferocytic pathways. Within these tissues, the macrophages also acquired features of human fetal cardiac macrophages. This reciprocal interaction provides a foundation for engineering macrophage functions, improving human tissue models and testing strategies to support cardiac repair.

We bring complementary expertise in mouse genetics, inducible lineage tracing, conditional gene deletion and experimental models of myocardial infarction, hypertension and viral myocarditis. These tools allow us to distinguish resident from recruited macrophages and test the contributions of specific cell populations and pathways to disease. We combine these approaches with human tissue studies, immune cell phenotyping, single-cell and single-nucleus transcriptomics, and spatial analysis.

Our interests also extend to the environmental signals that shape macrophage identity and function. Access to a wild mouse facility creates opportunities to investigate how diverse microbial exposures and the microbiome influence tissue immunity and disease susceptibility. We are also investigating macrophage interactions with microplastics, including whether particle exposure alters lysosomal function, inflammatory responses or tissue repair.

We can contribute to collaborative work packages involving the incorporation of macrophages into human tissue models, functional evaluation of engineered immune cells, and mechanistic testing in mice. We welcome partners with expertise in tissue engineering, biomaterials, stem cell biology, cell and gene engineering, microbiome science, environmental exposures and therapeutic development. We are particularly interested in projects that connect an improved understanding of macrophage biology with measurable gains in tissue function or resilience to injury.