Student Award for Outstanding Research Winner in the Ph.D. Category for the 9th World Biomaterials Congress, Chengdu, China, June 1-5, 2012: The interplay of bone-like extracellular matrix and TNF-α signaling on in vitro osteogenic differentiation of mesenchymal stem cells.

Student Award for Outstanding Research Winner in the Ph.D. Category for the 9th World Biomaterials Congress, Chengdu, China, June 1-5, 2012: The interplay of bone-like extracellular matrix and TNF-α signaling on in vitro osteogenic differentiation of mesenchymal stem cells.
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DOI:
10.1002/jbm.a.34058
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发表时间:
2012-05
影响因子:
4.9
通讯作者:
Mikos, Antonios G.
Mikos, Antonios G.
中科院分区:
工程技术3区
文献类型:
--
作者:
Mountziaris, Paschalia M.;Tzouanas, Stephanie N.;Mikos, Antonios G.

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作为合理控制炎症的骨组织工程策略开发的第一步,我们研究了骨样细胞外基质(ECM)和不同剂量的炎性细胞因子肿瘤坏死因子α(TNF-α)对体外培养在含有预生成骨样ECM的3D聚(ε-己内酯)(PCL)微纤维支架上的成骨分化间充质干细胞(MSC)的相互作用。为了产生ECM,PCL支架用MSC接种,并在含有通常所需的成骨补充剂地塞米松的培养基中培养。然而,由于地塞米松拮抗TNF-α,因此通过在不存在地塞米松的脱细胞支架上培养幼稚MSC来研究ECM和TNF-α的相互作用。在ECM涂层支架上培养的MSC继续存款矿化基质,这是成骨分化的晚期标志。暴露于TNF-α 4-8天未对矿化基质沉积产生不良影响,但连续暴露于TNF-α 16天后矿化基质沉积显著减少,这模拟了体内反应,其中短暂的TNF-α信号传导刺激骨再生,而长期暴露具有损伤作用。这强调了PCL/ECM构建体作为临床上更现实的体外培养模型的令人兴奋的潜力,以促进合理控制炎症以促进再生的新骨组织工程策略的设计。
As an initial step in the development of a bone tissue engineering strategy to rationally control inflammation, we investigated the interplay of bone-like extracellular matrix (ECM) and varying doses of the inflammatory cytokine tumor necrosis factor alpha (TNF-α) on osteogenically differentiating mesenchymal stem cells (MSCs) cultured in vitro on 3D poly(ε-caprolactone) (PCL) microfiber scaffolds containing pregenerated bone-like ECM. To generate the ECM, PCL scaffolds were seeded with MSCs and cultured in medium containing the typically required osteogenic supplement dexamethasone. However, since dexamethasone antagonizes TNF-α, the interplay of ECM and TNF-α was investigated by culturing naïve MSCs on the decellularized scaffolds in the absence of dexamethasone. MSCs cultured on ECM-coated scaffolds continued to deposit mineralized matrix, a late stage marker of osteogenic differentiation. Mineralized matrix deposition was not adversely affected by exposure to TNF-α for 4–8 days, but was significantly reduced after continuous exposure to TNF-α over 16 days, which simulates the in vivo response, where brief TNF-α signaling stimulates bone regeneration, while prolonged exposure has damaging effects. This underscores the exciting potential of PCL/ECM constructs as a more clinically realistic in vitro culture model to facilitate the design of new bone tissue engineering strategies that rationally control inflammation to promote regeneration.
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