title: Stem/progenitor cell-mediated de novo regeneration of dental pulp with newly deposited continuous layer of dentin in an in vivo model.
abstract: The ultimate goal of this study is to regenerate lost dental pulp and dentin via stem/progenitor cell-based approaches and tissue engineering technologies. In this study, we tested the possibility of regenerating vascularized human dental pulp in emptied root canal space and producing new dentin on existing dentinal walls using a stem/progenitor cell-mediated approach with a human root fragment and an immunocompromised mouse model. Stem/progenitor cells from apical papilla and dental pulp stem cells were isolated, characterized, seeded onto synthetic scaffolds consisting of poly-D,L-lactide/glycolide, inserted into the tooth fragments, and transplanted into mice. Our results showed that the root canal space was filled entirely by a pulp-like tissue with well-established vascularity. In addition, a continuous layer of dentin-like tissue was deposited onto the canal dentinal wall. This dentin-like structure appeared to be produced by a layer of newly formed odontoblast-like cells expressing dentin sialophosphoprotein, bone sialoprotein, alkaline phosphatase, and CD105. The cells in regenerated pulp-like tissue reacted positively to anti-human mitochondria antibodies, indicating their human origin. This study provides the first evidence showing that pulp-like tissue can be regenerated de novo in emptied root canal space by stem cells from apical papilla and dental pulp stem cells that give rise to odontoblast-like cells producing dentin-like tissue on existing dentinal walls.
authors.affiliation: Section of Oral and Diagnostic Sciences, Division of Endodontics, College of Dental Medicine, Columbia University, New York, New York, USA. gtjhuang@bu.edu
authors.forename: George T-J
authors.initials: GT
authors.lastname: Huang
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Yamaza
authors.forename: Lonnie D
authors.initials: LD
authors.lastname: Shea
authors.forename: Farida
authors.initials: F
authors.lastname: Djouad
authors.forename: Nastaran Z
authors.initials: NZ
authors.lastname: Kuhn
authors.forename: Rocky S
authors.initials: RS
authors.lastname: Tuan
authors.forename: Songtao
authors.initials: S
authors.lastname: Shi
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003771:Dental Papilla / Q000166:cytology; D003782:Dental Pulp / Q000098:blood supply / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D003786:Dental Pulp Cavity / Q000166:cytology; D003804:Dentin / Q000378:metabolism*; D000939:Epitopes; D006801:Humans; D007150:Immunohistochemistry; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D008954:Models, Biological; D009804:Odontoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011098:Polyglactin 910 / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D054457:Tissue Scaffolds; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000939:Epitopes; D011956:Receptors, Cell Surface; D011098:Polyglactin 910