title: Effects of Stem Cell Factor on Cell Homing During Functional Pulp Regeneration in Human Immature Teeth.
abstract: Conventional root canal treatment in immature permanent teeth can lead to early tooth loss in children because root formation is discontinued. We investigated whether the stem cell factor (SCF) could facilitate cell homing in the pulpless immature root canal and promote regeneration of a functional pulp. In vitro, human mesenchymal stem cells (hMSCs) were exposed to SCF at various concentrations for assessing cell migration, proliferation, and differentiation toward odonto/osteoblasts by 3D-chemotaxis slides, WST-1 assay, and alkaline phosphatase activity, respectively. Fibrin gels were used to deliver 15 μg/mL SCF for in vivo experiments. The release kinetic of SCF was assessed in vitro. Two corresponding human immature premolars, with or without SCF, were placed at rat calvariae for 6 and 12 weeks. All tooth specimens were either analyzed histologically and the percentage of tissue ingrowth determined or the cells were extracted from the pulp space, and the mRNA level of DMP1, DSPP, Col1, NGF, and VEGF were assessed by quantitative polymerase chain reaction. In the presence of SCF, we saw an increase in hMSCs directional migration, proliferation, and odonto/osteogenic differentiation. SCF also increased the extent of tissue ingrowth at 6 weeks but not at 12 weeks. However, at this time point, the formed tissue appeared more mature in samples with SCF. In terms of gene transcription, DMP1, Col1, and VEGF were the significantly upregulated genes, while DSPP and NGF were not affected. Our results suggest that SCF can accelerate cell homing and the maturation of the pulp-dentin complex in human immature teeth.
authors.affiliation: 1 Oral Biotechnology and Bioengineering, Center of Dental Medicine, University of Zürich , Zürich, Switzerland .|2 Zurich Center for Integrative Human Physiology (ZIHP), University of Zürich , Zürich, Switzerland .|3 Department of Pharmacology, Faculty of Dentistry, Mahidol University , Bangkok, Thailand .
authors.forename: Nisarat
authors.initials: N
authors.lastname: Ruangsawasdi
authors.affiliation: 4 Clinic for Preventive Dentistry, Periodontology, and Cariology, University of Zürich , Zürich, Switzerland .
authors.forename: Matthias
authors.initials: M
authors.lastname: Zehnder
authors.affiliation: 5 Clinic for Orthodontics and Pediatric Dentistry, Center of Dental Medicine, University of Zürich , Zürich, Switzerland .
authors.forename: Raphael
authors.initials: R
authors.lastname: Patcas
authors.affiliation: 1 Oral Biotechnology and Bioengineering, Center of Dental Medicine, University of Zürich , Zürich, Switzerland .
authors.forename: Chafik
authors.initials: C
authors.lastname: Ghayor
authors.affiliation: 1 Oral Biotechnology and Bioengineering, Center of Dental Medicine, University of Zürich , Zürich, Switzerland .|2 Zurich Center for Integrative Human Physiology (ZIHP), University of Zürich , Zürich, Switzerland .
authors.forename: Barbara
authors.initials: B
authors.lastname: Siegenthaler
authors.affiliation: 1 Oral Biotechnology and Bioengineering, Center of Dental Medicine, University of Zürich , Zürich, Switzerland .
authors.forename: Bebeka
authors.initials: B
authors.lastname: Gjoksi
authors.affiliation: 1 Oral Biotechnology and Bioengineering, Center of Dental Medicine, University of Zürich , Zürich, Switzerland .|2 Zurich Center for Integrative Human Physiology (ZIHP), University of Zürich , Zürich, Switzerland .
authors.forename: Franz E
authors.initials: FE
authors.lastname: Weber
mesh_terms: D000293:Adolescent; D001641:Bicuspid / Q000293:injuries / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects*; D002648:Child; D003782:Dental Pulp / Q000166:cytology / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D012038:Regeneration / Q000187:drug effects*; D019089:Stem Cell Factor / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019089:Stem Cell Factor
keywords: cell homing; immature permanent tooth; pulp regeneration; stem cell factor