title: SCF promotes dental pulp progenitor migration, neovascularization, and collagen remodeling - potential applications as a homing factor in dental pulp regeneration.
abstract: Stem cell factor (SCF) is a powerful chemokine that binds to the c-Kit receptor CD117 and has shown promise as a homing agent capable of progenitor cell recruitment. In the present study we have documented high levels of both SCF and its receptor c-Kit in differentiating dental pulp (DP) cells and in the sub-odontoblastic layer of Höhl. In vitro studies using human DP progenitors revealed a significant increase in cell proliferation after100 nM SCF application, explained by a 2-fold upregulation in cyclin D3 and FGF2 cell cycle regulators, and a 7-fold increase in CDK4 expression. DP cell migration in the presence of SCF was up-regulated 2.7-fold after a 24 h culture period, and this effect was accompanied by cytoskeletal rearrangement, a 1.5-fold increase in polymeric F-actin over G-actin, and a 1.8-fold increase in RhoA expression. Explaining the signaling effect of SCF on DP migration, PI3K/Akt and MEK/ERK pathway inhibitors were demonstrated to significantly reduce DP cell migration, while SCF alone doubled the number of migrated cells. ERK and AKT phosphorylation were dramatically upregulated already 3-5 min after SCF addition to the culture medium and declined thereafter, classifying SCF as a fast acting chemokine. When applied as an agent to promote tissue regeneration in subcutaneously implanted collagen sponges, SCF resulted in a 7-fold increase in the cell number in the implanted tissue construct, a more than 9-fold increase in capillaries, as well as collagen sponge remodeling and collagen fiber neogenesis. Together, these studies demonstrate the suitability of SCF as a potent aid in the regeneration of dental pulp and other mesenchymal tissues, capable of inducing cell homing, angiogenesis, and tissue remodeling.
authors.affiliation: School of Dentistry, Department of Endodontics, Harbin Medical University, Harbin, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Pan
authors.forename: Smit
authors.initials: S
authors.lastname: Dangaria
authors.forename: Gokul
authors.initials: G
authors.lastname: Gopinathan
authors.forename: Xiulin
authors.initials: X
authors.lastname: Yan
authors.forename: Xuanyu
authors.initials: X
authors.lastname: Lu
authors.forename: Antonia
authors.initials: A
authors.lastname: Kolokythas
authors.forename: Yumei
authors.initials: Y
authors.lastname: Niu
authors.forename: Xianghong
authors.initials: X
authors.lastname: Luan
mesh_terms: D000293:Adolescent; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D003094:Collagen / Q000378:metabolism*; D056743:Cyclin D3 / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D003782:Dental Pulp / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D019089:Stem Cell Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D014183:Transplantation, Heterologous
chemical_list: D056743:Cyclin D3; D019089:Stem Cell Factor; D003094:Collagen; D019869:Phosphatidylinositol 3-Kinases; D019009:Proto-Oncogene Proteins c-kit; D051358:Cyclin-Dependent Kinase 4; D048049:Extracellular Signal-Regulated MAP Kinases