Painting factor H onto mesenchymal stem cells protects the cells from complement- and neutrophil-mediated damage.
Painting factor H onto mesenchymal stem cells protects the cells from complement- and neutrophil-mediated damage.
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DOI：
10.1016/j.biomaterials.2016.05.055
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发表时间：
2016-09
期刊：
影响因子：
14
通讯作者：
Lin F
中科院分区：
文献类型：
--
作者：
Li Y;Qiu W;Zhang L;Fung J;Lin F
间充质干细胞（MSCs）作为一种有前景的治疗多种炎症性疾病和再生医学的新疗法，正在进行大量的临床试验，但目前基于间充质干细胞的治疗方法还需要进一步优化。在这项研究中，我们发现，除了我们和其他人最近报道的通过膜攻击复合物（MACs）组装的补体介导的直接攻击外，释放的补体激活产物C5a，而不是C3a，激活血液中的中性粒细胞，通过氧化破裂进一步损伤MSCs。此外，我们还开发了一种简单的方法，将天然补体抑制剂因子H涂在MSCs上，以局部抑制MSCs上的补体活化。在体内和体外，用因子H修饰的间充质干细胞可以免受MAC和中性粒细胞介导的攻击，并且比模拟修饰的间充质干细胞更有效地抑制抗原特异性T细胞反应。
Mesenchymal stem cells (MSCs) are undergoing intensive testing in clinical trials as a promising new therapy for many inflammatory diseases and for regenerative medicine, but further optimization of current MSC-based therapies is required. In this study, we found that in addition to direct complement–mediated attack through the assembly of membrane attack complexes (MACs) that we and others have recently reported, of the released complement activation products, C5a, but not C3a, activates neutrophils in the blood to further damage MSCs through oxidative burst. In addition, we have developed a simple method for painting factor H, a native complement inhibitor, onto MSCs to locally inhibit complement activation on MSCs. MSCs painted with factor H are protected from both MAC- and neutrophil-mediated attack and are significantly more effective in inhibiting antigen-specific T cell responses than the mock-painted MSCs both in vitro and in vivo.