牙髓生物学的发展使得牙髓再生获得越来越多的关注。对于牙髓坏死或者根尖周病变的年轻恒牙来说，根管内的牙髓已感染坏死，没有可用的自体牙髓干细胞，而存在于根尖周的根尖牙乳头干细胞尚可能存活，利用趋化因子将根尖牙乳头干细胞迁移入根管内实现牙髓再生成为可能。本项目组的前期研究结果已经证实SDF-1/CXCR4可介导根尖牙乳头干细胞发生迁移，但根尖牙乳头干细胞表面CXCR4表达很低，SDF-1条件下，CXCR4如何转运至细胞表面，其具体机制尚不清楚。本研究拟考察生理条件下CXCR4在根尖牙乳头干细胞内的分布和定位，并研究SDF-1条件下，根尖牙干细胞CXCR4表达分布的变化。本研究对于揭示SDF-1/CXCR4介导根尖牙乳头干细胞迁移的机制有重要意义，从而为根尖牙乳头干细胞介导的年轻恒牙牙髓再生奠定基础。

Regenerative endodontics has gained attention due to the development of pulp biology. When the pulp is lost in an immature tooth resulting from necrosis, dental pulp stem cells (DPSCs) are no longer present. In cases where apical papilla is still viable, stem cells residing in the apical papilla (SCAP) may be present and could be attracted into the canal space to regenerate the pulp. Previously we have demonstrated that stem cells from apical papilla (SCAP) can be chemoattracted by stromal cell-derived factor-1 (SDF-1)/CXCR4. However, the cell surface expression of CXCR4, which is the functional state of CXCR4, is very low in SCAP. How could CXCR4 translocate from intracellular compartments to cell surface under SDF-1 induction, and how could SDF-1/CXCR4 activate downstream signaling pathway is unknown. Thus the aim of this project is to investigate the subcellular localization, and the mechanism involved in SDF-1/CXCR4 mediated SCAP migration. The findings of this project may provide insights into the mechanisms that underlie SDF-1α-mediated migration of SCAP, thus to provide evidence for dental pulp regeneration of young permanent teeth via cell homing.

利用趋化因子将根尖牙乳头干细胞迁移入根管内是实现牙髓再生的一种可能途径。本项目组的前期研究结果证实CXCR4主要分布在根尖牙乳头干细胞内，细胞表面表达很低。SDF-1/CXCR4可介导根尖牙乳头干细胞发生迁移。但CXCR4在根尖牙乳头干细胞内如何分布及定位、如何转运至细胞表面，其具体机制尚不清楚。本研究考察了生理条件下CXCR4在根尖牙乳头干细胞中的分布和定位，发现CXCR4主要分布在早期胞内体、循环胞内体及溶酶体内。进一步采用内吞抑制剂预处理细胞抑制CXCR4的胞内循环后，发现人根尖牙乳头干细胞表面CXCR4表达增加，且SDF-1介导的人根尖牙乳头干细胞迁移增加，但细胞增殖未见显著改变，提示细胞迁移增加确实为细胞表面CXCR4表达增加所致。本研究结果对于揭示CXCR4的胞内循环途径调节细胞膜表面CXCR4表达机制有重要意义，同时为采用药物处理方法从而增加根尖牙乳头干细胞迁移的新策略提供依据。