Co-treating mesenchymal stem cells with IL-1β and TNF-α increases VCAM-1 expression and improves post-ischemic myocardial function

Abstract

Inflammatory mediators are released by the myocardium following myocardial ischemia as a response to tissue injury, and contribute to cardiac repair and adaptive responses. Treating mesenchymal stem cells (MSCs) with various inflammatory factors activates a series of biological processes that enhance cell-mediated cardioprotection following myocardial infarction (MI). The present study was designed to examine the effect of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) treatment on vascular cell adhesion molecule-1 (VCAM-1) expression in MSCs, and to identify whether cytokine-treated MSCs improve post-ischemic myocardial function in a rat model. MSCs were stimulated with IL-1β and/or TNF-α for 24 h, the production of vascular cell adhesion molecule-1 (VCAM-1) and the adhesion ability of MSCs were assessed by flow cytometry, adhesion assays, quantitative polymerase chain reaction and western blot analysis. The cardiac function was examined by two-dimensional echocardiography. The results demonstrated that in treated MSCs, the secretion of VCAM-1 and the cell adhesion ability were significantly increased, thus markedly improving cardiac function compared with that of the control group (P<0.01). Of all the groups, the rats stimulated with a combination of IL-1β and TNF-α exhibited the greatest cardiac improvements. However, there was no significant difference between the 10 and 20 ng/ml groups which were stimulated with one of the cytokines alone (P>0.05). In conclusion, stimulating MSCs with IL-1β and TNF-α promoted the expression of VCAM-1 and improved post-ischemic cardiac function recovery. Treating MSCs with two cytokines in combination may be a useful method to maximize the potential of cell-based therapy for MI.