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.

Perivascular Ancestors of Adult Multipotent Stem Cells

“…Two exceptions to this are the ability of pericytes to regenerate chemoablated Leydig cells in the rat testis 69 and white adipocyte progenitors belonging to the mural cell compartment in mouse adipose tissue vasculature. 56 These observations must be confirmed within multiple other cell lineages before a generalized role of perivascular cells in tissue homeostasis can be concluded. Nevertheless, as previously illustrated, perivascular cells are strong candidates for medical tissue regeneration, even before expansion in culture into MSC-like 72 and are, therefore, candidate trophic "drugstore" cells.…”

“…9,15,[55][56][57] These discoveries imply that pericytes can potentially be applied to bone regeneration, dental repair, and adipose reconstruction.…”

Fibrin Gel Improves Tissue Ingrowth and Cell Differentiation in Human Immature Premolars Implanted in Rats

“…In the presence of a fibrin gel, structured tissues similar to normal pulp were observed after 12 weeks of implantation. Previous studies demonstrated either adipose tissues or ectopic mineral deposition in the canal space of whole teeth or tooth fragments implanted in rodents (9,21). A recent study in immature, formerly infected teeth in dogs, suggested that an injectable scaffold is unnecessary for pulp regeneration.…”

Scaffolds in Regenerative Endodontics: A Review.

“…Tooth like structures have been obtained by seeding dental pulp stem cells on PLGA scaffolds. [62] Bioactive ceramics:-Calcium phosphate ceramics such as hydroxyapatite (HA), betatricalcium phosphate (β-TCP), and biphasic calcium phosphate (BCP) are totally biocompatible and bioactive crystallized materials. [63,64] Cells cultured on the porous form of ceramics could attach, proliferate, and expressed dentin sialophosphoprotein, which is a dentin marker.…”