title: 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.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Cariology, Endodontology and Operative Dentistry, School and Hospital of Stomatology, Peking University, Beijing, People's Republic of China.
authors.forename: Jing-Yi
authors.initials: JY
authors.lastname: Liu
authors.affiliation: Department of Cariology, Endodontology and Operative Dentistry, School and Hospital of Stomatology, Peking University, Beijing, People's Republic of China.
authors.forename: Xue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Cariology, Endodontology and Operative Dentistry, School and Hospital of Stomatology, Peking University, Beijing, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yue
authors.affiliation: Department of Bioscience Research, College of Dentistry, University of Tennessee Health Science Center, Memphis, Tennessee.
authors.forename: George T-J
authors.initials: GT
authors.lastname: Huang
authors.affiliation: Department of Cariology, Endodontology and Operative Dentistry, School and Hospital of Stomatology, Peking University, Beijing, People's Republic of China. Electronic address: zouxiaoying1125@163.com.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Zou
mesh_terms: D000293:Adolescent; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism*; D002633:Chemotaxis; D003782:Dental Pulp / Q000502:physiology; D003804:Dentin / Q000502:physiology; D006801:Humans; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012038:Regeneration; D013234:Stem Cells / Q000166:cytology*; D019227:Tooth Apex / Q000166:cytology* / Q000378:metabolism*; D055815:Young Adult
chemical_list: D054377:Chemokine CXCL12; D019718:Receptors, CXCR4
keywords: 3-dimensional transmigration assay; CXC chemokine receptor 4; cell homing; stem cells from the apical papilla; stromal cell–derived factor-1α