title: SHED differentiate into functional odontoblasts and endothelium.
abstract: Studies on mechanisms underlying the differentiation of dental pulp stem cells are critical for the understanding of the biology of odontogenesis and for dental tissue engineering. Here, we tested the hypothesis that stem cells from exfoliated deciduous teeth (SHED) differentiate into functional odontoblasts and endothelial cells. SHED were seeded in tooth slice/scaffolds and implanted subcutaneously into immunodeficient mice. SHED differentiated into functional odontoblasts that generated tubular dentin, as determined by tetracycline staining and confocal microscopy. These cells also differentiated into vascular endothelial cells, as determined by beta-galactosidase staining of LacZ-tagged SHED. In vitro, vascular endothelial growth factor (VEGF) induced SHED to express VEGFR2, CD31, and VE-Cadherin (markers of endothelium) and to organize into capillary-like sprouts. VEGF induced ERK and AKT phosphorylation (indicative of differentiation), while inhibiting phosphorylation of STAT3 (indicative of 'stemness'). Collectively, this work demonstrates that SHED can differentiate into angiogenic endothelial cells and odontoblasts capable of generating tubular dentin.
authors.affiliation: Department of Pediatric Dentistry, Orthodontics and Community Health, Bauru School of Dentistry, University of São Paulo, Brazil.
authors.forename: V T
authors.initials: VT
authors.lastname: Sakai
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: Z
authors.initials: Z
authors.lastname: Dong
authors.forename: K G
authors.initials: KG
authors.lastname: Neiva
authors.forename: M A A M
authors.initials: MA
authors.lastname: Machado
authors.forename: S
authors.initials: S
authors.lastname: Shi
authors.forename: C F
authors.initials: CF
authors.lastname: Santos
authors.forename: J E
authors.initials: JE
authors.lastname: Nör
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D003782:Dental Pulp / Q000166:cytology*; D003804:Dentin / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009804:Odontoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010750:Phosphoproteins / Q000096:biosynthesis; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012795:Sialoglycoproteins / Q000096:biosynthesis; D040521:Subcutaneous Tissue; D054457:Tissue Scaffolds; D014094:Tooth, Deciduous / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000502:physiology; D000099311:Dentin Sialophosphoprotein
chemical_list: D016326:Extracellular Matrix Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D010750:Phosphoproteins; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D012795:Sialoglycoproteins; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1; D000099311:Dentin Sialophosphoprotein; C513309:DMP1 protein, human