Tooth Slice/Scaffold Model of Dental Pulp Tissue Engineering

Department of Cariology, Restorative Sciences and Endodontics, University of Michigan School of Dentistry, Ann Arbor, 48109-1078, USA.
Advances in dental research 07/2011; 23(3):325-32. DOI: 10.1177/0022034511405325
Source: PubMed


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.

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    • "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). "
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    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.
    Full-text · Article · Jan 2014 · Frontiers in Physiology
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    • "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. "
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    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.
    Full-text · Article · Nov 2013 · Journal of Dental Research
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    • "Regeneration of dental pulp tissues is the ultimate goal of biological endodontics[11], while periodontal regeneration serves to provide new and healthy attachment for diseased teeth[12,13]. In previous studies, pulp tissues were regenerated using a pulp-slice model141516or subcutaneous implants[11]to demonstrate the regenerative capability of dental pulp stem cells[17]. In contrast, recent cell homing studies exploited the chemotactic effects of SDF-1 to recruit dental pulp-like cells into collagen scaffolds or subcutaneously implanted tooth roots, or other cells into the periphery of anatomically shaped tooth scaffolds[9]. "
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    ABSTRACT: Stem cell factor (SCF) is a powerful chemokine that binds to the c-Kit receptor CD117 and has shown promise as a homing agent capable of progenitor cell recruitment. In the present study we have documented high levels of both SCF and its receptor c-Kit in differentiating dental pulp (DP) cells and in the sub-odontoblastic layer of Höhl. In vitro studies using human DP progenitors revealed a significant increase in cell proliferation after100 nM SCF application, explained by a 2-fold upregulation in cyclin D3 and FGF2 cell cycle regulators, and a 7-fold increase in CDK4 expression. DP cell migration in the presence of SCF was up-regulated 2.7-fold after a 24 h culture period, and this effect was accompanied by cytoskeletal rearrangement, a 1.5-fold increase in polymeric F-actin over G-actin, and a 1.8-fold increase in RhoA expression. Explaining the signaling effect of SCF on DP migration, PI3K/Akt and MEK/ERK pathway inhibitors were demonstrated to significantly reduce DP cell migration, while SCF alone doubled the number of migrated cells. ERK and AKT phosphorylation were dramatically upregulated already 3-5 min after SCF addition to the culture medium and declined thereafter, classifying SCF as a fast acting chemokine. When applied as an agent to promote tissue regeneration in subcutaneously implanted collagen sponges, SCF resulted in a 7-fold increase in the cell number in the implanted tissue construct, a more than 9-fold increase in capillaries, as well as collagen sponge remodeling and collagen fiber neogenesis. Together, these studies demonstrate the suitability of SCF as a potent aid in the regeneration of dental pulp and other mesenchymal tissues, capable of inducing cell homing, angiogenesis, and tissue remodeling.
    Full-text · Article · May 2013 · Stem cell reviews
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