Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates.
Colony stimulating factor-1 receptor is a central component of the foreign body response to biomaterial implants in rodents and non-human primates.
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DOI：
10.1038/nmat4866
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发表时间：
2017-06
期刊：
影响因子：
41.2
通讯作者：
Anderson DG
中科院分区：
文献类型：
--
作者：
Doloff JC;Veiseh O;Vegas AJ;Tam HH;Farah S;Ma M;Li J;Bader A;Chiu A;Sadraei A;Aresta-Dasilva S;Griffin M;Jhunjhunwala S;Webber M;Siebert S;Tang K;Chen M;Langan E;Dholokia N;Thakrar R;Qi M;Oberholzer J;Greiner DL;Langer R;Anderson DG
生物材料的宿主识别和免疫介导的异物反应(FBR)会影响植入式医疗设备的性能。为了确定关键的细胞和细胞因子靶点，我们在这里对啮齿动物和非人灵长类动物体内植入的生物材料的先天和获得性免疫系统反应进行了深入的系统分析。虽然巨噬细胞在纤维化的级联中是不可或缺的，但令人惊讶的是，中性粒细胞和补体却不是。巨噬细胞通过CXCL13导致下游B细胞募集，进一步加强了纤维化，B细胞敲除和CXCL13中和证实了这一点。有趣的是，在植入多种生物材料后，集落刺激因子-1受体(CSF1R)显著增加：陶瓷、聚合物和水凝胶。它的抑制，就像巨噬细胞耗尽一样，导致纤维化的完全消失，但保留了其他巨噬细胞的功能，如伤口愈合，ROS产生和吞噬。我们的结果表明，靶向CSF1R可能允许一种更具选择性的抑制纤维化的方法，并改善生物材料的生物相容性，而不需要广泛的免疫抑制。
Host recognition and immune-mediated foreign body response (FBR) to biomaterials can compromise the performance of implanted medical devices. To identify key cell and cytokine targets, here we perform in-depth systems analysis of innate and adaptive immune system responses to implanted biomaterials in rodents and non-human primates. While macrophages are indispensable to the fibrotic cascade, surprisingly neutrophils and complement are not. Macrophages, via CXCL13, lead to downstream B cell recruitment, which further potentiated fibrosis, as confirmed by B cell knock out and CXCL13 neutralization. Interestingly, Colony Stimulating Factor-1 Receptor (CSF1R) is significantly increased following implantation of multiple biomaterial classes: ceramic, polymer, and hydrogel. Its inhibition, like macrophage depletion, leads to complete loss of fibrosis, but spares other macrophage functions such as wound healing, ROS production, and phagocytosis. Our results indicate targeting CSF1R may allow for a more selective method of fibrosis inhibition, and improve biomaterial biocompatibility without the need for broad immunosuppression.