Dose effect of tumor necrosis factor-alpha on in vitro osteogenic differentiation of mesenchymal stem cells on biodegradable polymeric microfiber scaffolds.
Dose effect of tumor necrosis factor-alpha on in vitro osteogenic differentiation of mesenchymal stem cells on biodegradable polymeric microfiber scaffolds.
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DOI：
10.1016/j.biomaterials.2009.11.058
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发表时间：
2010-03
期刊：
影响因子：
14
通讯作者：
Mikos, Antonios G.
中科院分区：
文献类型：
--
作者：
Mountziaris, Paschalia M.;Tzouanas, Stephanie N.;Mikos, Antonios G.
这项研究提出了骨组织工程策略发展的第一步，通过调节炎症来触发增强骨生成。这项工作的重点是表征促炎细胞因子，肿瘤坏死因子α（TNF-α）的浓度对在3D培养系统中生长的间充质干细胞（MSC）的成骨分化的影响。MSC成骨分化通常通过成骨补充剂的组合在体外实现，所述成骨补充剂包括抗炎皮质类固醇地塞米松。虽然简单，但地塞米松的使用在临床上并不现实，并且还阻碍了炎症介质在伤口愈合中的作用的体外研究。在这项研究中，用地塞米松预处理MSC以诱导成骨分化，然后在可生物降解的电纺聚（ε-己内酯）（PCL）支架中培养，该支架在没有地塞米松的情况下支持MSC继续成骨分化。连续给予0.1ng/mL重组大鼠TNF-α抑制大鼠MSCs的成骨分化超过16天，这可能是残留地塞米松拮抗TNF-α信号传导的结果。连续输送较高剂量（5 ng/mL TNF-α）可刺激成骨分化数天，50 ng/mL TNF-α在研究过程中导致显著矿化基质沉积。这些研究结果表明，促炎细胞因子TNF-α刺激MSC的成骨分化，这种作用可以被抗炎剂如地塞米松的存在所阻断，对炎症和组织再生之间的相互作用具有重要意义。
This study presents a first step in the development of a bone tissue engineering strategy to trigger enhanced osteogenesis by modulating inflammation. This work focused on characterizing the effects of the concentration of a pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α), on osteogenic differentiation of mesenchymal stem cells (MSCs) grown in a 3D culture system. MSC osteogenic differentiation is typically achieved in vitro through a combination of osteogenic supplements that include the anti-inflammatory corticosteroid dexamethasone. Although simple, the use of dexamethasone is not clinically realistic, and also hampers in vitro studies of the role of inflammatory mediators in wound healing. In this study, MSCs were pre-treated with dexamethasone to induce osteogenic differentiation, and then cultured in biodegradable electrospun poly(ε-caprolactone) (PCL) scaffolds, which supported continued MSC osteogenic differentiation in the absence of dexamethasone. Continuous delivery of 0.1 ng/mL of recombinant rat TNF-α suppressed osteogenic differentiation of rat MSCs over 16 days, which was likely the result of residual dexamethasone antagonizing TNF-α signaling. Continuous delivery of a higher dose, 5 ng/mL TNF-α, stimulated osteogenic differentiation for a few days, and 50 ng/mL TNF-α resulted in significant mineralized matrix deposition over the course of the study. These findings suggest that the pro-inflammatory cytokine TNF-α stimulates osteogenic differentiation of MSCs, an effect that can be blocked by the presence of anti-inflammatory agents like dexamethasone, with significant implications on the interplay between inflammation and tissue 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：
Iqbal, Jameel;Li Sun;Zaidi, Mone
通讯作者：
Zaidi, Mone
影响因子：
4.8
作者：
Gilbert, L;He, XF;Nanes, MS
通讯作者：
Nanes, MS
影响因子：
--
作者：
Gomes, ME;Bossano, CM;Mikos, AG
通讯作者：
Mikos, AG
DOI：
10.1016/b978-0-12-372578-3.00012-x
发表时间：
2008-01-01
期刊：
MICROSCOPE IMAGE PROCESSING
影响因子：
--
作者：
Merchant, Fatima A.;Periasamy, Ammasi
通讯作者：
Periasamy, Ammasi
影响因子：
4.1
作者：
Martins, Ana M.;Pham, Quynh P.;Mikos, Antonios G.
通讯作者：
Mikos, Antonios G.