title: Interferon Gamma-treated Dental Pulp Stem Cells Promote Human Mesenchymal Stem Cell Migration In Vitro.
abstract: BACKGROUND
  Chronic inflammation disrupts dental pulp regeneration by disintegrating the recruitment process of progenitors for repair. Bone marrow-derived mesenchymal stem cells (BM-MSCs) share the common features with dental pulp stem cells (DPSCs). The aim of the study was to investigate the migration of BM-MSCs toward DPSCs in response to inflammatory chemoattractants. Additionally, our studies also delineated the signaling mechanisms from BM-MSCs in mediating the proliferation and differentiation of DPSCs in vitro.
  
  
  METHODS
  Human DPSCs and BM-MSCs between passages 2 and 4 were used and were grown in odontogenic differentiation medium. Mineralization was determined by alizarin red staining analysis. Migration was assessed using crystal violet staining in cells grown in Boyden chamber Transwell inserts (Corning Inc Foundation, Tewksbury, MA). The mineralization potential of DPSCs was evaluated using alkaline phosphatase activity assay. Real-time polymerase chain reaction analysis was performed to assess the gene expression profile of chemokine (C-X-C motif) ligand (Cxcl) 3, 5, 6, 10, 11, 12, 14, and 16; stromal cell-derived factor (SDF) α; vascular endothelial growth factor; and fibroblast growth factor.
  
  
  RESULTS
  Interferon gamma (FN-γ) treatment significantly abrogated the differentiation potential of DPSCs as shown by using alizarin red and alkaline phosphatase activity analysis. An increase in the migration of BM-MSCs was documented when cocultured with IFN-γ-treated DPSCs. RNA expression studies showed an increase in the levels of Cxcl6 and Cxcl12 in BM-MSCs when cocultured with IFN-γ-treated DPSCs. Additionally, an up-regulation of proangiogenic factors vascular endothelial growth factor and fibroblast growth factor were observed in DPSCs exposed to IFN-γ.
  
  
  CONCLUSIONS
  Our findings indicate that inflamed IFN-γ-treated DPSCs release factors (presumably Cxcl6 and 12) that contribute to the homing of MSCs. This model might provide a potential research tool for studying MSC-DPSC cross talk and for future studies involving the recruitment and sustainability of progenitor stem cells sustaining the inflammatory cascade to treat pulp inflammation.
authors.affiliation: Department of Endodontics, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Chelsee
authors.initials: C
authors.lastname: Strojny
authors.affiliation: Department of Endodontics, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Michael
authors.initials: M
authors.lastname: Boyle
authors.affiliation: Department of Surgery, College of Medicine, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Amelia
authors.initials: A
authors.lastname: Bartholomew
authors.affiliation: Department of Endodontics, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois; Department of Surgery, College of Medicine, University of Illinois at Chicago, Chicago, Illinois.
authors.forename: Premanand
authors.initials: P
authors.lastname: Sundivakkam
authors.affiliation: Department of Endodontics, College of Dentistry, University of Illinois at Chicago, Chicago, Illinois; Department of Surgery, College of Medicine, University of Illinois at Chicago, Chicago, Illinois. Electronic address: salapati@uic.edu.
authors.forename: Satish
authors.initials: S
authors.lastname: Alapati
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D002113:Calcification, Physiologic / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D019743:Chemokines, CXC / Q000378:metabolism; D018920:Coculture Techniques; D003470:Culture Media; D003782:Dental Pulp / Q000166:cytology / Q000276:immunology*; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000276:immunology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D019743:Chemokines, CXC; D003470:Culture Media; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D005346:Fibroblast Growth Factors; D007371:Interferon-gamma; D000469:Alkaline Phosphatase
keywords: Bone marrow–derived mesenchymal stem cells; dental pulp stem cells; inflammation; interferon-γ; migration; regenerative endodontics