Human amnion mesenchymal stem cells attenuate atherosclerosis by modulating macrophage function to reduce immune response

Abstract

Mesenchymal stem cells (MSCs) show immunosuppressive activities and alleviate atherosclerosis (AS) formation in apolipoprotein E.knockout (apoE-KO) mice. Human amnion mesenchymal stem cells (hAMSCs), a particular population of mesenchymal stem cells, have been shown to have immunomodulatory abilities. The present study investigated the effects of hAMSCs treatment on early atherosclerotic plaque formation and the progression of established lesion in apoE-KO mice. In total, 36 mice were fed with a high-fat diet. Mice were subjected to hAMSCs-injection treatment simultaneously with high-fat diet (early treatment) or after 8 weeks of high-fat diet (delayed treatment). In each treatment, mice were divided into three groups: i) hAMSCs group with hAMSCs treatment; ii) PBS group injected with PBS; and iii) control group without injection. Histological results showed that the plaque area in the aortic arch of mice was significantly reduced after hAMSCs treatment in the early and delayed treatment groups. In addition, immunohistochemical analysis suggested that the accumulation of macrophages was significantly decreased after hAMSCs treatment. Similarly, the release of the pro-inflammatory cytokine tumor necrosis factor-α was also decreased, whereas the release of the anti.inflammatory cytokine interleukin-10 was increased. In addition, hAMSCs treatment suppressed the phosphorylation of p65 and inhibitor of κB-α, suggesting that NF-κB pathway was involved in the hAMSCs-mediated suppression of immune response. In conclusion, hAMSCs treatment was effective in reducing immune response, which is the one of the major causes of AS, eventually leading to a significant reduction in size of atherosclerotic lesions.