ArticleStem cell research & therapy2025
Mesenchymal stromal cells modulate neutrophil phenotype via paracrine signals.
Article in Stem cell research & therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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12 authors.
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Abstract
backgroundDespite the recognized importance of neutrophils in cardiac repair following myocardial infarction (MI), their interaction with mesenchymal stromal cells (MSCs), particularly regarding polarization phenotypes and functional impacts, remains unclear. Here, we investigated these interactions across controlled in vitro systems and an in vivo MI model.
methodsHuman HL-60 cells were differentiated into neutrophil-like cells (dHL-60) and polarized toward N1/N2 states to test the MSC paracrine effects using indirect transwell coculture. Readouts included gene expression, cytokine profiling and functional assays. To increase translational relevance, indirect ex vivo cocultures of human MSCs with primary neutrophils isolated from MI mice or from MI patients were analysed for gene expression and cytokine profiles in conditioned media. In vivo, syngeneic mouse MSCs were transplanted subcutaneously immediately after MI, and early cardiac function was evaluated by echocardiography. Cardiac neutrophils where quantified by flow cytometry, and Ly6G
resultsIn vitro, MSCs suppressed pro-inflammatory mediators in N1-like neutrophils and enhanced reparative factors in N2-like cells. In vivo, remote MSC transplantation improved early cardiac performance, and reduced neutrophil accumulation in the infarct. Paradoxically, cardiac neutrophils showed transcriptomic enrichment of inflammatory pathways, whereas blood neutrophils showed reduced interferon-related programs.
conclusionOur findings indicate that MSCs can modulate neutrophil responses, underscoring the nuanced effects of MSC-based approaches in ischemic heart disease. These results suggest that anti-inflammatory effects observed under controlled conditions may not fully translate in vivo, highlighting the importance of context when evaluating MSC-based therapies.
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