Efficient induction of functional ameloblasts from human keratinocyte stem cells.
Efficient induction of functional ameloblasts from human keratinocyte stem cells.
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从人角质形成细胞干细胞中有效诱导功能性成釉细胞
DOI：
10.1186/s13287-018-0822-4
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发表时间：
2018-05-02
影响因子：
7.5
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Hu X;Lee JW;Zheng X;Zhang J;Lin X;Song Y;Wang B;Hu X;Chang HH;Chen Y;Lin CP;Zhang Y
成年人组织来源的表皮干细胞与具有成牙潜能的小鼠牙间充质细胞重组后，虽然能够分化为分泌釉质的成釉细胞并形成具有再生釉质的牙齿，但诱导率相对较低。此外，再生牙釉质是否保持与人牙釉质相同的棱柱运行模式，并获得与人牙釉质相当的机械性能，确实值得进一步研究。将培养的人角质形成细胞干细胞（hKSCs）用成纤维细胞生长因子8（FGF 8）和Sonic hedgehog（SHH）处理18 h或36 h，然后与E13.5小鼠牙间充质重组，将FGF 8和SHH浸泡的琼脂糖珠植入重建的嵌合牙胚中。重组牙胚在裸鼠肾被膜中培养。处理在不同时间点收获的样品用于组织学、免疫组织化学、TUNEL和蛋白质印迹分析。利用扫描电镜和纳米压痕测试分析再生牙釉质的棱镜运行模式和力学性能。在组织重组之前用FGF 8和SHH两者处理hKSC将齿状结构形成的速率大大提高至约70%。FGF 8和SHH显著增强培养的hKSC的干细胞性。扫描电子显微镜分析显示再生牙釉质完整棱柱的运行模式与人牙釉质相似。纳米压痕测试表明，虽然比人类儿童和成年小鼠釉质柔软得多，但再生釉质的机械性能随着培养时间的延长而改善。在培养的hKSC中应用FGF 8和SHH蛋白改善了干细胞性，但不促进hKSC的牙源性命运，导致hKSC的成釉细胞分化和人-小鼠嵌合牙胚中牙齿形成的效率提高。本文的在线版本（10.1186/s13287-018-0822-4）包含补充材料，可供授权用户使用。
Although adult human tissue-derived epidermal stem cells are capable of differentiating into enamel-secreting ameloblasts and forming teeth with regenerated enamel when recombined with mouse dental mesenchyme that possesses odontogenic potential, the induction rate is relatively low. In addition, whether the regenerated enamel retains a running pattern of prism identical to and acquires mechanical properties comparable with human enamel indeed warrants further study. Cultured human keratinocyte stem cells (hKSCs) were treated with fibroblast growth factor 8 (FGF8) and Sonic hedgehog (SHH) for 18 h or 36 h prior to being recombined with E13.5 mouse dental mesenchyme with implantation of FGF8 and SHH-soaked agarose beads into reconstructed chimeric tooth germs. Recombinant tooth germs were subjected to kidney capsule culture in nude mice. Harvested samples at various time points were processed for histological, immunohistochemical, TUNEL, and western blot analysis. Scanning electronic microscopy and a nanoindentation test were further employed to analyze the prism running pattern and mechanical properties of the regenerated enamel. Treatment of hKSCs with both FGF8 and SHH prior to tissue recombination greatly enhanced the rate of tooth-like structure formation to about 70%. FGF8 and SHH dramatically enhanced stemness of cultured hKSCs. Scanning electron microscopic analysis revealed the running pattern of intact prisms of regenerated enamel is similar to that of human enamel. The nanoindentation test indicated that, although much softer than human child and adult mouse enamel, mechanical properties of the regenerated enamel improved as the culture time was extended. Application of FGF8 and SHH proteins in cultured hKSCs improves stemness but does not facilitate odontogenic fate of hKSCs, resulting in an enhanced efficiency of ameloblastic differentiation of hKSCs and tooth formation in human–mouse chimeric tooth germs. The online version of this article (10.1186/s13287-018-0822-4) contains supplementary material, which is available to authorized users.
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DOI：
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发表时间：
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期刊：
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