Regenerative endodontics in light of the stem cell paradigm

Abstract

Stem cells play a critical role in development and in tissue regeneration. The dental pulp contains a small sub-population of stem cells that are involved in the response of the pulp to caries progression. Specifically, stem cells replace odontoblasts that have undergone cell death as a consequence of the cariogenic challenge. Stem cells also secrete factors that have the potential to enhance pulp vascularisation and provide the oxygen and nutrients required for the dentinogenic response that is typically observed in teeth with deep caries. However, the same angiogenic factors that are required for dentine regeneration may ultimately contribute to the demise of the pulp by enhancing vascular permeability and interstitial pressure. Recent studies focused on the biology of dental pulp stem cells revealed that the multipotency and angiogenic capacity of these cells could be exploited therapeutically in dental pulp tissue engineering. Collectively, these findings suggest new treatment paradigms in the field of endodontics. The goal of this review is to discuss the potential impact of dental pulp stem cells to regenerative endodontics.

© 2011 FDI World Dental Federation.

Figures

Figure 1.

Expression of VEGF by dental pulp cells. Photomicrographs at low (A) and high (B) magnification of VEGF immunohistochemistry from the rat dental pulp. Intense VEGF staining is observed in the odontoblastic and sub-odontoblastic layers. Legends: periodontal ligament (PDL), dental pulp (DP), dentine (D), odontoblastic layer (OD), sub-odontoblastic layer (SOD). (C) Baseline VEGF expression in murine cell lines: undifferentiated dental pulp cells (OD-21), odontoblasts-like cells (MDPC-23), and macrophages. (D) Baseline VEGF expression in human primary cells: dental pulp stem cells from permanent teeth (DPSC), human dental pulp fibroblasts (HDPF), and human dermal microvascular endothelial cells (HDMEC).

Figure 2.

Pilot study on VEGF and VEGFR2 expression in the pulp of sound and carious teeth. VEGF and VEGFR2 gene expression was analysed by RT-PCR in the dental pulp of two patients (patient A and B). Each pair consists of one tooth with a deep caries lesion and a non-carious tooth. VEGF was upregulated in the pulps of carious teeth as compared to the pulps from non-carious teeth. VEGFR2 expression was low in the pulp from one tooth with deep caries (patient A), and undetectable by RT-PCR in the remaining samples analysed here.

Figure 3.

Expression of TLR4 in dental pulp cells. Immunohistochemistry for TLR4 gene expression analysis (A, C, E, G) using a non-specific IgG as control (B, D, F, H). TLR4 was observed in the dental pulp stem cells (DPSC), human dental pulp fibroblasts (HDPF), rat odontoblast-like cells (MDPC-23), and mouse macrophages (control).

Figure 4.

Engineering of a dental pulp-like tissue in the root canal of a human tooth extracted for orthodontic reasons. Photomicrographs at low (A) and high (B) magnification of the tissue generated by the transplantation of SHED loaded in an injectable scaffold (Puramatrix) into the root canal of a human tooth transplanted into the subcutaneous space of an immunodeficient mouse.