Mesenchymal Stem Cells Reduce Murine Atherosclerosis Development.
Mesenchymal Stem Cells Reduce Murine Atherosclerosis Development.
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DOI：
10.1038/srep15559
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发表时间：
2015-10-22
影响因子：
4.6
通讯作者：
de Jager SC
中科院分区：
文献类型：
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作者：
Frodermann V;van Duijn J;van Pel M;van Santbrink PJ;Bot I;Kuiper J;de Jager SC
间充质干细胞（MSC）具有再生特性，但最近发现它们也具有免疫调节能力。因此，我们研究了MSC是否可以减少动脉粥样硬化，这是由血脂异常和慢性炎症决定的。我们将骨髓间充质干细胞过继转移到低密度脂蛋白受体敲除小鼠中，并将这些小鼠置于西式饮食中以诱导动脉粥样硬化。最初治疗后，我们发现更高水平的循环调节性T细胞。从长远来看，MSC治疗减少了效应T细胞的总数。此外，MSC处理的小鼠显示循环单核细胞显著减少33%，血清CCL 2水平降低77%。最引人注目的是，我们发现了一种以前未被重视的对脂质代谢的影响。由于极低密度脂蛋白水平降低，血清胆固醇降低了33%，这可能是通过硬脂酰辅酶A去饱和酶-1和脂蛋白脂肪酶表达降低确定的从头肝脂肪生成减少的结果。MSC显著影响病变发展，在主动脉根部减少了33%。这些病变包含的巨噬细胞减少了56%，T细胞数量减少了61%。我们在这里首次表明，MSC治疗不仅影响炎症反应，而且还显着减少小鼠血脂异常。这使得MSC成为动脉粥样硬化治疗的有效候选者。
Mesenchymal stem cells (MSCs) have regenerative properties, but recently they were also found to have immunomodulatory capacities. We therefore investigated whether MSCs could reduce atherosclerosis, which is determined by dyslipidaemia and chronic inflammation. We adoptively transferred MSCs into low-density lipoprotein-receptor knockout mice and put these on a Western-type diet to induce atherosclerosis. Initially after treatment, we found higher levels of circulating regulatory T cells. In the long-term, overall numbers of effector T cells were reduced by MSC treatment. Moreover, MSC-treated mice displayed a significant 33% reduction in circulating monocytes and a 77% reduction of serum CCL2 levels. Most strikingly, we found a previously unappreciated effect on lipid metabolism. Serum cholesterol was reduced by 33%, due to reduced very low-density lipoprotein levels, likely a result of reduced de novo hepatic lipogenesis as determined by a reduced expression of Stearoyl-CoA desaturase-1 and lipoprotein lipase. MSCs significantly affected lesion development, which was reduced by 33% in the aortic root. These lesions contained 56% less macrophages and showed a 61% reduction in T cell numbers. We show here for the first time that MSC treatment affects not only inflammatory responses but also significantly reduces dyslipidaemia in mice. This makes MSCs a potent candidate for atherosclerosis therapies.