Bone regeneration by human dental pulp stem cells using a helioxanthin derivative and cell-sheet technology.
Bone regeneration by human dental pulp stem cells using a helioxanthin derivative and cell-sheet technology.
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DOI：
10.1186/s13287-018-0783-7
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发表时间：
2018-02-01
影响因子：
7.5
通讯作者：
Chikazu D
中科院分区：
文献类型：
--
作者：
Fujii Y;Kawase-Koga Y;Hojo H;Yano F;Sato M;Chung UI;Ohba S;Chikazu D
人牙髓干细胞（DPSC）具有分化为多种细胞系的能力，最近被发现。DPSC可以很容易地从离体牙齿中收集，并且现在被认为是一种比骨髓干细胞（BMSCs）具有更高克隆形成和增殖潜力的间充质干细胞。与此同时，严重骨缺损的治疗，如骨折，癌症和先天性畸形，仍然是一个巨大的挑战，新的骨再生技术备受期待。以前的一些研究表明，4-（4-甲氧基苯基）吡啶并[40，30：4，5]噻吩并[2，3-B]吡啶-2-甲酰胺（TH），一种向日葵黄素衍生物，诱导前成骨细胞和间充质细胞的成骨分化。然而，TH的成骨分化活性仅在一些小鼠细胞系中得到证实。因此，在本研究中，针对TH在人体中的临床应用，我们分析了TH对DPSCs的成骨分化的影响，以及TH诱导的DPSCs的体内成骨能力，利用使用细胞片技术的简单移植系统。从5名健康患者（18-22岁）的智齿牙髓中获得DPSCs，并在常规培养基和含或不含TH的成骨培养基中培养。为了评估TH诱导的DPSC在体内的成骨作用，我们将DPSC片移植到小鼠颅骨缺损中。我们证明，与TH的成骨条件诱导DPSCs的成骨分化比那些没有TH和骨形态发生蛋白-2的更有效。而常规TH培养液不能诱导DPSCs向成骨细胞分化。TH诱导DPSC和BMSCs的成骨，虽然DPSC中的基因表达模式与TH诱导后14天的BMSCs不同。此外，我们成功地在体内使用DPSC片与TH治疗，而不使用任何支架或生长因子的骨再生。我们的研究结果表明，TH诱导的DPSC是骨再生医学的有用的细胞来源，和TH处理的DPSC片移植是一种方便的无支架骨愈合方法。本文的在线版本（10.1186/s13287-018-0783-7）包含补充材料，可供授权用户使用。
Human dental pulp stem cells (DPSCs), which have the ability to differentiate into multiple lineages, were recently identified. DPSCs can be collected readily from extracted teeth and are now considered to be a type of mesenchymal stem cell with higher clonogenic and proliferative potential than bone marrow stem cells (BMSCs). Meanwhile, the treatment of severe bone defects, such as fractures, cancers, and congenital abnormalities, remains a great challenge, and novel bone regenerative techniques are highly anticipated. Several studies have previously shown that 4-(4-methoxyphenyl)pyrido[40,30:4,5]thieno[2,3-b]pyridine-2-carboxamide (TH), a helioxanthin derivative, induces osteogenic differentiation of preosteoblastic and mesenchymal cells. However, the osteogenic differentiation activities of TH have only been confirmed in some mouse cell lines. Therefore, in this study, toward the clinical use of TH in humans, we analyzed the effect of TH on the osteogenic differentiation of DPSCs, and the in-vivo osteogenesis ability of TH-induced DPSCs, taking advantage of the simple transplantation system using cell-sheet technology. DPSCs were obtained from dental pulp of the wisdom teeth of five healthy patients (18–22 years old) and cultured in regular medium and osteogenic medium with or without TH. To evaluate osteogenesis of TH-induced DPSCs in vivo, we transplanted DPSC sheets into mouse calvaria defects. We demonstrated that osteogenic conditions with TH induce the osteogenic differentiation of DPSCs more efficiently than those without TH and those with bone morphogenetic protein-2. However, regular medium with TH did not induce the osteogenic differentiation of DPSCs. TH induced osteogenesis in both DPSCs and BMSCs, although the gene expression pattern in DPSCs differed from that in BMSCs up to 14 days after induction with TH. Furthermore, we succeeded in bone regeneration in vivo using DPSC sheets with TH treatment, without using any scaffolds or growth factors. Our results demonstrate that TH-induced DPSCs are a useful cell source for bone regenerative medicine, and the transplantation of DPSC sheets treated with TH is a convenient scaffold-free method of bone healing. The online version of this article (10.1186/s13287-018-0783-7) contains supplementary material, which is available to authorized users.
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影响因子：
5.2
作者：
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通讯作者：
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影响因子：
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Bagnara, GP