Multipotency is a defining characteristic of post-natal stem cells. The human dental pulp contains a small subpopulation of stem cells that exhibit multipotency, as demonstrated by their ability to differentiate into odontoblasts, neural cells, and vascular endothelial cells. These discoveries highlight the fundamental role of stem cells in the biology of the dental pulp and suggest that these cells are uniquely suited for dental pulp tissue-engineering purposes. The availability of experimental approaches specifically designed for studies of the differentiation potential of dental pulp stem cells has played an important role in these discoveries. The objective of this review is to describe the development and characterization of the Tooth Slice/Scaffold Model of Dental Pulp Tissue Engineering. In addition, we discuss the multipotency of dental pulp stem cells, focusing on the differentiation of these cells into functional odontoblasts and into vascular endothelial cells.
"In order to engineer the dental pulp tissue successfully, the choice of stem cells, scaffolds and growth factors is paramount. Several recent publications, have shown the ability of different dental cell types with both natural and artificial polymeric scaffolds and growth factors to regenerate dental pulp-like tissue in a subcutaneous implantation model (Cordeiro et al., 2008; Alsanea et al., 2011; Huang, 2011; Sakai et al., 2011). However, more recently, CD105 positive and CD31 negative dental pulp cells along with collagen and stromal derived factor 1 (SDF1) were used to regenerate the dental pulp in a canine pulpectomy model (Iohara et al., 2011; Ishizaka et al., 2012). "
[Show abstract][Hide abstract] ABSTRACT: Dental Caries affects approximately 90% of the world's population. At present, the clinical treatment for dental caries is root canal therapy. This treatment results in loss of tooth sensitivity and vitality. Tissue engineering can potentially solve this problem by enabling regeneration of a functional pulp tissue. Dental pulp stem cells (DPSCs) have been shown to be an excellent source for pulp regeneration. However, limited availability of these cells hinders its potential for clinical translation. We have investigated the possibility of using somatic mesenchymal stem cells (MSCs) from other sources for dental pulp tissue regeneration using a biomimetic dental pulp extracellular matrix (ECM) incorporated scaffold. Human periodontal ligament stem cells (PDLSCs) and human bone marrow stromal cells (HMSCs) were investigated for their ability to differentiate toward an odontogenic lineage. In vitro real-time PCR results coupled with histological and immunohistochemical examination of the explanted tissues confirmed the ability of PDLSCs and HMSCs to form a vascularized pulp-like tissue. These findings indicate that the dental pulp stem derived ECM scaffold stimulated odontogenic differentiation of PDLSCs and HMSCs without the need for exogenous addition of growth and differentiation factors. This study represents a translational perspective toward possible therapeutic application of using a combination of somatic stem cells and extracellular matrix for pulp regeneration.
Frontiers in Physiology 01/2014; 4:395. DOI:10.3389/fphys.2013.00395 · 3.53 Impact Factor
"Stem cells from human exfoliated deciduous teeth (SHED) are highly proliferative and capable of generating a dental pulp-like tissue and to differentiate into odontoblasts (Miura et al., 2003; Cordeiro et al., 2008; Casagrande et al., 2010; Chadipiralla et al., 2010) and endothelial cells (Sakai et al., 2010; Bento et al., 2013). Proof-of-principle experiments have used fairly rigid scaffolds, as for example poly(L-lactic acid (PLLA), cast within tooth slices and transplanted into mice (Cordeiro et al., 2008; Sakai et al., 2011). Although such a strategy provides valuable mechanistic information on the potential of dental pulp stem cells in pulp regeneration, it presents shortcomings: (A) The use of tooth slices does not take into full account the three-dimensional geometry of root canals. "
[Show abstract][Hide abstract] ABSTRACT: The clinical translation of stem-cell-based dental pulp regeneration will require the use of injectable scaffolds. Here, we tested the hypothesis that stem cells from exfoliated deciduous teeth (SHED) can generate a functional dental pulp when injected into full-length root canals. SHED survived and began to express putative markers of odontoblastic differentiation after 7 days when mixed with Puramatrix™ (peptide hydrogel), or after 14 days when mixed with recombinant human Collagen (rhCollagen) type I, and injected into the root canals of human premolars in vitro. Roots of human premolars injected with scaffolds (Puramatrix™ or rhCollagen) containing SHED were implanted subcutaneously into immunodeficient mice (CB-17 SCID). We observed pulp-like tissues with odontoblasts capable of generating new tubular dentin throughout the root canals. Notably, the pulp tissue engineered with SHED injected with either Puramatrix™ or rhCollagen type I presented similar cellularity and vascularization when compared with control human dental pulps. Analysis of these data, collectively, demonstrates that SHED injected into full-length human root canals differentiate into functional odontoblasts, and suggests that such a strategy might facilitate the completion of root formation in necrotic immature permanent teeth.
Journal of Dental Research 11/2013; 92(11):970. DOI:10.1177/0022034513505772 · 4.14 Impact Factor
"It has been documented that the tooth slice is an available culture model of the dentin-pulp complex (Sloan et al. 1998). Recently, several human tooth slice models allowed the regeneration of dentin/pulp-like tissues and neo-angiogenesis inside the pulp cavity (Huang et al. 2010; Sakai et al. 2011). In the current study, 5-mm length tooth segments at the radicular portion with opened both end-sides were designed for favorable angiogenesis conditions. "
[Show abstract][Hide abstract] ABSTRACT: Pulp regeneration using human dental pulp stem cells (hDPSCs) maintains tooth vitality compared with conventional root canal therapy. Our previous study demonstrated that preameloblast-conditioned medium (PA-CM) from murine apical bud cells induces the odontogenic differentiation of hDPSCs and promoted dentin formation in mouse subcutaneous tissue. The purpose of the present study is to evaluate the effects of PA-CM with human whole pulp cells on pulp regeneration in an empty root canal space. Human pulp cells were seeded in the pulp cavities of 5 mm-thick human tooth segments with or without PA-CM treatment, and then transplanted subcutaneously into immunocompromised mice. In the pulp cell-only group, skeletal muscle with pulp-like tissue was generated in the pulp cavity. A reparative dentin-like structure with entrapped cells lined the existing dentin wall. However, in the PA-CM-treated group, only pulp-like tissue was regenerated without muscle or a reparative dentin-like structure. Moreover, human odontoblast-like cells exhibited palisade arrangement around the pulp, and typical odontoblast processes elongated into dentinal tubules. The results suggest that PA-CM can induce pulp regeneration of human pulp cells with physiological structures in an empty root canal space.
Journal of molecular histology 05/2013; DOI:10.1007/s10735-013-9513-8 · 1.82 Impact Factor
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