CXC Chemokine Receptor 4 Is Expressed Paravascularly in Apical Papilla and Coordinates with Stromal Cell-derived Factor-1 α during Transmigration of Stem Cells from Apical Papilla

CXC Chemokine Receptor 4 Is Expressed Paravascularly in Apical Papilla and Coordinates with Stromal Cell-derived Factor-1 α during Transmigration of Stem Cells from Apical Papilla
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DOI:
10.1016/j.joen.2015.04.006
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发表时间:
2015-09-01
影响因子:
4.2
通讯作者:
Zou, Xiao-Ying
Zou, Xiao-Ying
中科院分区:
医学2区
文献类型:
--
作者:
Liu, Jing-Yi;Chen, Xue;Zou, Xiao-Ying

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简介:根尖部的根尖乳头干细胞(SCAPs)可能被吸引到根管间隙中,作为牙髓-牙本质再生的细胞来源。为了测试这种可能性,我们使用体外迁移模型来研究SCAPs是否可以通过递送趋化细胞因子基质细胞衍生因子-1 α(SDF-1 α)而被化学吸引。研究方法:我们首先使用免疫荧光、逆转录聚合酶链反应(RT-PCR)和流式细胞术分析检测了CXC趋化因子受体4(CXCR 4)在顶乳头和培养的SCAPs中SDF-1 α的表达。使用标准Transwell迁移测定和三维细胞迁移测定来分析SCAPs经由SDF-1 α/CXCR 4轴的迁移。结果:CXCR 4在根尖乳头血管旁区表达,并在SCAP培养中检测到。大多数培养的SCAPs具有细胞内CXCR 4(58%-99%,n = 4),而只有少数细胞在细胞表面上具有可检测的CXCR 4(0.3%-2.34%,n = 4)。虽然SDF-1 α对SCAP增殖没有显著影响,但它显著促进了更多的迁移细胞;抗CXCR 4抗体消除了这种影响。有趣的是,SCAPs上的细胞表面CXCR 4直到迁移后才被检测到。三维迁移试验显示SDF-1 α显著增强胶原凝胶中的SCAP迁移。结论:SCAPs可以通过SDF-1 α/CXCR 4轴被化学吸引,这表明SDF-1 α可以在临床上用于诱导根尖乳头中表达CXCR 4的SCAPs迁移到根管间隙中,作为牙髓再生的内源性细胞来源。
Introduction: Stem cells from the apical papilla (SCAPs) at the apex may be attracted into the root canal space as a cell source for pulp-dentin regeneration. To test this possibility, we used in vitro transmigration models to investigate whether SCAPs can be chemoattracted by the delivery of the chemotactic cytokine stromal cell derived factor-1 alpha (SDF-1 alpha). Methods: We first examined the expression of CXC chemokine receptor 4 (CXCR4) for SDF-1 alpha in the apical papilla and in cultured SCAPs using immunofluorescence, reverse-transcription polymerase chain reaction (RT-PCR), and flow cytometric analyses. A standard Transwell migration assay and a 3-dimensional cell migration assay were used to analyze transmigration of SCAPs via the SDF-1 alpha/CXCR4 axis. Results: CXCR4 was expressed in the paravascular region of the apical papilla and detected in SCAP cultures. Most cultured SCAPs harbored intracellular CXCR4 (58%-99%, n = 4), whereas only a few cells had detectable CXCR4 on the cell surface (0.3%-2.34%, n = 4). Although SDF-1 alpha had no significant effect on SCAP proliferation, it significantly promoted a higher number of migrated cells; this effect was abolished by anti-CXCR4 antibodies. Interestingly, cell surface CXCR4 on SCAPs was not detectable until after transmigration. The 3-dimensional migration assay revealed that SDF-1 alpha significantly enhanced SCAP migration in the collagen gel. Conclusions: SCAPs can be chemoattracted via the SDF-1 alpha/CXCR4 axis, suggesting that SDF-1 alpha may be used clinically to induce CXCR4expressing SCAPs in the apical papilla to transmigrate into the root canal space as an endogenous cell source for pulp regeneration.