Immunomodulation by mesenchymal stem cells combats the foreign body response to cell-laden synthetic hydrogels.
Immunomodulation by mesenchymal stem cells combats the foreign body response to cell-laden synthetic hydrogels.
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DOI：
10.1016/j.biomaterials.2014.11.020
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发表时间：
2015-03
期刊：
影响因子：
14
通讯作者：
Bryant SJ
中科院分区：
文献类型：
--
作者：
Swartzlander MD;Blakney AK;Amer LD;Hankenson KD;Kyriakides TR;Bryant SJ
植入非生物材料，包括组织工程支架，普遍导致异物反应（FBR）。我们最近报告说，这种反应对合成水凝胶中包裹的成纤维细胞产生负面影响，反过来导致更严重的FBR，这表明包裹的细胞和炎症细胞之间存在串扰。鉴于间充质干细胞（MSC）在组织工程中的前景和最近的证据表明其免疫调节特性，我们假设，包封在聚（乙二醇）（PEG）水凝胶中的MSC将减弱FBR。在体外，包封在PEG水凝胶中的鼠MSC通过减少促炎细胞因子（最显著的是肿瘤坏死因子-α）的基因表达和蛋白分泌来减弱经典活化的原代鼠巨噬细胞。使用COX 2抑制剂，前列腺素E2（PGE 2）被确定为MSC免疫调节巨噬细胞的介质。在体内，将载有MSC、成骨分化MSC或无细胞的水凝胶皮下植入C57 BL/6小鼠28天，以评估MSC对FBR纤维化反应的影响。与无细胞水凝胶相比，包封的MSC的存在降低了纤维囊厚度，但这种作用随着成骨分化而减弱。因此，在组织工程中分化之前使用MSC可以作为一种动态方法，通过MSC和炎性细胞之间的连续串扰来调节巨噬细胞活化并减弱FBR到植入的合成支架，从而改善长期组织工程结果。
The implantation of non-biological materials, including scaffolds for tissue engineering, ubiquitously leads to a foreign body response (FBR). We recently reported that this response negatively impacts fibroblasts encapsulated within a synthetic hydrogel and in turn leads to a more severe FBR, suggesting a cross-talk between encapsulated cells and inflammatory cells. Given the promise of mesenchymal stem cells (MSCs) in tissue engineering and recent evidence of their immunomodulatory properties, we hypothesized that MSCs encapsulated within poly(ethylene glycol) (PEG) hydrogels will attenuate the FBR. In vitro, murine MSCs encapsulated within PEG hydrogels attenuated classically activated primary murine macrophages by reducing gene expression and protein secretion of pro-inflammatory cytokines, most notably tumor necrosis factor-α. Using a COX2 inhibitor, prostaglandin E2 (PGE2) was identified as a mediator of MSC immunomodulation of macrophages. In vivo, hydrogels laden with MSCs, osteogenically differentiating MSCs, or no cells were implanted subcutaneously into C57BL/6 mice for 28 days to assess the impact of MSCs on the fibrotic response of the FBR. The presence of encapsulated MSCs reduced fibrous capsule thickness compared to acellular hydrogels, but this effect diminished with osteogenic differentiation. The use of MSCs prior to differentiation in tissue engineering may therefore serve as a dynamic approach, through continuous cross-talk between MSCs and the inflammatory cells, to modulate macrophage activation and attenuate the FBR to implanted synthetic scaffolds thus improving the long-term tissue engineering outcome.
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影响因子：
5.2
作者：
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