Effect of temporally patterned TNF-α delivery on in vitro osteogenic differentiation of mesenchymal stem cells cultured on biodegradable polymer scaffolds.
Effect of temporally patterned TNF-α delivery on in vitro osteogenic differentiation of mesenchymal stem cells cultured on biodegradable polymer scaffolds.
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DOI：
10.1080/09205063.2013.803455
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Mikos AG
中科院分区：
文献类型：
--
作者：
Mountziaris PM;Dennis Lehman E;Mountziaris I;Sing DC;Kasper FK;Mikos AG
近年来，对促炎症细胞因子，特别是肿瘤坏死因子-α(Tumor-NectorFor-α)在骨再生中的关键作用的深入研究，预示着骨组织工程构建的设计将是一个新的方向。以往的研究表明，将50 ng/ml肿瘤坏死因子-α持续输送到三维可生物降解的电纺聚己内酯微纤维网架上的间充质干细胞，可刺激矿化基质沉积，这是成骨分化的标志。由于肿瘤坏死因子-α在体内骨折后呈现双相表达，本研究的目的是研究肿瘤坏死因子-α在三维电纺支架上表达的时间模式对骨髓间充质干细胞体外成骨分化的影响。MSCs培养16天，暴露于持续、早期、中期或晚期的肿瘤坏死因子-α。为了进一步阐明肿瘤坏死因子-α对成骨分化的影响，研究设计包括在存在和不存在典型的成骨补充剂地塞米松的情况下预培养的骨髓间充质干细胞。地塞米松-单纯骨髓间充质干细胞构建中未观察到矿化基质沉积，提示肿瘤坏死因子-α不足以触发骨髓间充质干细胞体外成骨分化。在地塞米松预培养的MSCs中，肿瘤坏死因子-α抑制成骨分化的早期标志碱性磷酸酶的活性，刺激成骨分化的晚期标志矿化基质的沉积。通过阐明肿瘤坏死因子-α递送的时间变化对骨髓间充质干细胞成骨分化的影响，我们的结果为深入了解肿瘤坏死因子-α的再生机制提供了必要的设计参数，并为合理控制肿瘤坏死因子-α信号以刺激骨再生的新的组织工程策略提供了必要的设计参数。
Recent insight into the critical role of pro-inflammatory cytokines, particularly tumor necrosis factor-α (TNF-α), in bone regeneration has heralded a new direction in the design of bone tissue engineering constructs. Previous studies have demonstrated that continuous delivery of 50 ng/ml TNF-α to mesenchymal stem cells (MSCs) cultured on three-dimensional (3D) biodegradable electrospun poly(ε-caprolactone) (PCL) microfiber meshes stimulates mineralized matrix deposition, a marker of osteogenic differentiation. Since TNF-α exhibits a biphasic pattern of expression following bone fracture in vivo, the goal of this study was to investigate the effects of temporal patterns of TNF-α delivery on in vitro osteogenic differentiation of MSCs cultured on 3D electrospun PCL scaffolds. MSCs were cultured for 16 days and exposed to continuous, early, intermediate, or late TNF-α delivery. To further elucidate the effects of TNF-α on osteogenic differentiation, the study design included MSCs pre-cultured both in the presence and absence of the typically required osteogenic supplement dexamethasone. Mineralized matrix deposition was not observed in constructs with dexamethasone-naïve MSCs, suggesting that TNF-α is not sufficient to trigger in vitro osteogenic differentiation of MSCs. For MSCs precultured with dexamethasone, TNF-α suppressed ALP activity, an early marker of osteogenic differentiation, and stimulated mineralized matrix deposition, a late stage marker of MSC osteogenic differentiation. By elucidating the impact of temporal variations in TNF-α delivery on MSC osteogenic differentiation, our results offer insight into the regenerative mechanism of TNF-α and provide the necessary design parameters for a novel tissue engineering strategy that rationally controls TNF-α signaling to stimulate bone regeneration.
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DOI：
10.1073/pnas.0606805103
发表时间：
2006-10-03
影响因子：
11.1
作者：
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影响因子：
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