Abstract
BackgroundHuman mesenchymal stromal cells (MSCs) have been reported to preserve cardiac function in myocardial infarction (MI) models. Previously, we found a beneficial effect of intramyocardial injection of unstimulated human MSCs (uMSCs) on cardiac function after permanent coronary artery ligation. In the present study we aimed to extend this research by investigating the effect of intramyocardial injection of human MSCs pre-stimulated with the pro-inflammatory cytokine interferon-gamma (iMSCs), since pro-inflammatory priming has shown additional salutary effects in multiple experimental disease models.MethodsMI was induced in NOD/Scid mice by permanent ligation of the left anterior descending coronary artery. Animals received intramyocardial injection of uMSCs, iMSCs or PBS. Sham-operated animals were used to determine baseline characteristics. Cardiac performance was assessed after 2 and 14 days using 7-Tesla magnetic resonance imaging and pressure-volume loop measurements. Histology and q-PCR were used to confirm MSC engraftment in the heart.ResultsBoth uMSC and iMSC therapy had no significant beneficial effect on cardiac function or remodelling in contrast to our previous studies.ConclusionsAnimal models for cardiac MSC therapy appear less robust than initially envisioned.
Highlights
Cardiovascular disease (CVD) is the main mortality cause in the western world [1]
In the present study we aimed to extend this research by assessing the effect of pre-stimulating the human mesenchymal stromal cells (MSCs) with the pro-inflammatory cytokine interferon gamma (IFN)
As myocardial infarction (MI) causes the influx of inflammatory cells into the injured myocardium [26], we investigated whether the inflammatory cell influx was altered by uMCs and iMSCs administration
Summary
Cardiovascular disease (CVD) is the main mortality cause in the western world [1]. Over the past decade, studies have explored the potential of cell therapy as a novel treatment option for coronary artery disease. We reported beneficial therapeutic effects of injection of unstimulated human MSCs (uMSCs) from CVD patients in a myocardial infarction (MI) model in NOD/Scid mice [4,19]. In the present study we aimed to extend this research by assessing the effect of pre-stimulating the human MSCs (iMSCs) with the pro-inflammatory cytokine interferon gamma (IFN). Human mesenchymal stromal cells (MSCs) have been reported to preserve cardiac function in myocardial infarction (MI) models. We found a beneficial effect of intramyocardial injection of unstimulated human MSCs (uMSCs) on cardiac function after permanent coronary artery ligation. In the present study we aimed to extend this research by investigating the effect of intramyocardial injection of human MSCs pre-stimulated with the pro-inflammatory cytokine interferon-gamma (iMSCs), since pro-inflammatory priming has shown additional salutary effects in multiple experimental disease models
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