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

• Published in: Journal of endodontics Vol. 41; no. 9; pp. 1430 - 1436
• Main Authors: Liu, Jing-Yi, DDS, Chen, Xue, DDS, Yue, Lin, DDS, PhD, Huang, George T.-J., DDS, MSD, DSc, Zou, Xiao-Ying, DDS, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2015
• Subjects: 3-dimensional transmigration assay; Adolescent; cell homing; Cells, Cultured; Chemokine CXCL12 - metabolism; Chemotaxis; CXC chemokine receptor 4; Dental Pulp - physiology; Dentin - physiology; Dentistry; Endocrinology & Metabolism; Humans; Receptors, CXCR4 - metabolism; Regeneration; Stem Cells - cytology; stem cells from the apical papilla; stromal cell–derived factor-1α; Tooth Apex - cytology; Tooth Apex - metabolism; Young Adult; stem cells from the apical papilla; 3-dimensional transmigration assay; cell homing; stromal cell–derived factor-1α; CXC chemokine receptor 4
• DOI: 10.1016/j.joen.2015.04.006
• ISSN: 0099-2399

Abstract 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-1α (SDF-1α). Methods We first examined the expression of CXC chemokine receptor 4 (CXCR4) for SDF-1α 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-1α/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-1α 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-1α significantly enhanced SCAP migration in the collagen gel. Conclusions SCAPs can be chemoattracted via the SDF-1α/CXCR4 axis, suggesting that SDF-1α may be used clinically to induce CXCR4-expressing SCAPs in the apical papilla to transmigrate into the root canal space as an endogenous cell source for pulp regeneration.