Adipose-derived mesenchymal stromal cells modulate tendon fibroblast responses to macrophage-induced inflammation in vitro.
Adipose-derived mesenchymal stromal cells modulate tendon fibroblast responses to macrophage-induced inflammation in vitro.
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DOI：
10.1186/s13287-015-0059-4
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发表时间：
2015-04-16
影响因子：
7.5
通讯作者：
Thomopoulos S
中科院分区：
文献类型：
--
作者：
Manning CN;Martel C;Sakiyama-Elbert SE;Silva MJ;Shah S;Gelberman RH;Thomopoulos S
巨噬细胞驱动的炎症是肌腱修复后早期的一个关键特征，但过度炎症与不良临床结局相关。使用分子或细胞治疗来调节炎症环境可以提供增强肌腱愈合的手段。为了研究巨噬细胞分泌的促炎细胞因子对肌腱成纤维细胞（TF）的影响，我们建立了细胞因子和巨噬细胞诱导的炎症体外模型。基因表达，蛋白质表达和细胞活力测定用于检查TF反应。为了减少炎性细胞因子对TF的负面影响，将脂肪来源的间充质基质细胞（ASC）纳入模型中，并研究其调节炎症的能力。炎性细胞因子白细胞介素1 β（IL-1β）和不同表型的巨噬细胞诱导促炎因子和基质降解因子的上调以及与培养物中TF形成细胞外基质相关的因子的下调。ASC不能抑制IL-1β诱导的这些可能的负面作用。然而，ASC与M1（促炎性）巨噬细胞共培养通过诱导从促炎性巨噬细胞表型到抗炎性巨噬细胞表型的表型转换成功地抑制了M1巨噬细胞对TF的作用，从而导致TF暴露于较低水平的促炎性细胞因子（例如，IL-1β，肿瘤坏死因子α（TNFα））。这些发现表明IL-1β和M1巨噬细胞对肌腱愈合有害，ASC介导的术后炎症反应调节可能有利于肌腱愈合。本文的在线版本（doi：10.1186/s13287-015-0059-4）包含补充材料，可供授权用户使用。
Macrophage-driven inflammation is a key feature of the early period following tendon repair, but excessive inflammation has been associated with poor clinical outcomes. Modulation of the inflammatory environment using molecular or cellular treatments may provide a means to enhance tendon healing. To examine the effect of pro-inflammatory cytokines secreted by macrophages on tendon fibroblasts (TF), we established in vitro models of cytokine and macrophage-induced inflammation. Gene expression, protein expression, and cell viability assays were used to examine TF responses. In an effort to reduce the negative effects of inflammatory cytokines on TFs, adipose-derived mesenchymal stromal cells (ASCs) were incorporated into the model and their ability to modulate inflammation was investigated. The inflammatory cytokine interleukin 1 beta (IL-1β) and macrophages of varying phenotypes induced up-regulation of pro-inflammatory factors and matrix degradation factors and down-regulation of factors related to extracellular matrix formation by TFs in culture. ASCs did not suppress these presumably negative effects induced by IL-1β. However, ASC co-culture with M1 (pro-inflammatory) macrophages successfully suppressed the effects of M1 macrophages on TFs by inducing a phenotypic switch from a pro-inflammatory macrophage phenotype to an anti-inflammatory macrophage phenotype, thus resulting in exposure of TFs to lower levels of pro-inflammatory cytokines (e.g., IL-1β, tumor necrosis factor alpha (TNFα)). These findings suggest that IL-1β and M1 macrophages are detrimental to tendon healing and that ASC-mediated modulation of the post-operative inflammatory response may be beneficial for tendon healing. The online version of this article (doi:10.1186/s13287-015-0059-4) contains supplementary material, which is available to authorized users.
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影响因子：
2.6
作者：
Kim, Jaehyup;Hematti, Peiman
通讯作者：
Hematti, Peiman
影响因子：
1.8
作者：
Berglund, M.;Hart, D. A.;Wiig, M.
通讯作者：
Wiig, M.
影响因子：
2.6
作者：
Bartholomew, A;Sturgeon, C;Hoffman, R
通讯作者：
Hoffman, R
DOI：
10.1302/0301-620x.82b7.9892
发表时间：
2000-09-01
影响因子：
--
作者：
Khan, U;Kakar, S;McGrouther, DA
通讯作者：
McGrouther, DA
影响因子：
4.4
作者：
Lucas, Tina;Waisman, Ari;Eming, Sabine A.
通讯作者：
Eming, Sabine A.