Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine

Emory University, United States of America
PLoS ONE (Impact Factor: 3.23). 02/2006; 1(1):e79. DOI: 10.1371/journal.pone.0000079
Source: PubMed


Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance.

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Available from: Wataru Sonoyama, Oct 01, 2015
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    • "We analyzed native mineralized tissues of teeth (enamel, dentin, and cementum) and used these measurements as comparison points for the biochemical characteristics of mineralized tissue formed in vitro by different dental mesenchymal cells grown in osteogenic medium. Human cell populations were isolated from different parts of the tooth and surrounding tissues that have been shown to have MSC properties in vitro (Gronthos et al. 2002; Miura et al. 2003; Seo et al. 2004; Sonoyama et al. 2006; Huang et al. 2009; Mitrano et al. 2010; Park et al. 2012). In addition, we included a source of cells (BCMP) isolated from the bone chip material obtained during dental implant procedures. "
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    ABSTRACT: Mesenchymal stem cells isolated from different dental tissues have been described to have osteogenic/odontogenic-like differentiation capacity, but little attention has been paid to the biochemical composition of the material that each produces. Here, we used Raman spectroscopy to analyze the mineralized materials produced in vitro by different dental cell populations, and we compared them with the biochemical composition of native dental tissues. We show that different dental stem cell populations produce materials that differ in their mineral and matrix composition and that these differ from those of native dental tissues. In vitro, BCMP (bone chip mass population), SCAP (stem cells from apical papilla), and SHED (stem cells from human-exfoliated deciduous teeth) cells produce a more highly mineralized matrix when compared with that produced by PDL (periodontal ligament), DPA (dental pulp adult), and GF (gingival fibroblast) cells. Principal component analyses of Raman spectra further demonstrated that the crystallinity and carbonate substitution environments in the material produced by each cell type varied, with DPA cells, for example, producing a more carbonate-substituted mineral and with SCAP, SHED, and GF cells creating a less crystalline material when compared with other dental stem cells and native tissues. These variations in mineral composition reveal intrinsic differences in the various cell populations, which may in turn affect their specific clinical applications. © International & American Associations for Dental Research 2015.
    Journal of dental research 08/2015; DOI:10.1177/0022034515599765 · 4.14 Impact Factor
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    • "This may due to the lack of critical inductive factors for root formation, which are abundant in natural dentin and TDM scaffolds [16]. While in the test group, well organized new tissues (Fig. 7) including pulpdentin complex inside the TDM scaffold and PDL-cementum complex outside showed the successful regeneration of tooth roots [10] [11] [13] [14], providing basis for post retained crown restoration and masticatory function. The regenerated roots sustained a well Fig. 8 "
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    ABSTRACT: Tooth root supports dental crown and bears occlusal force. While proper root shape and size render the force being evenly delivered and dispersed into jawbone. Yet it remains unclear what shape and size of a biological tooth root (bio-root), which is mostly determined by the scaffold geometric design, is suitable for stress distributing and mastication performing. Therefore, this study hypothesized scaffold fabricated in proper shape and size is better for regeneration of tooth root with approving biomechanical functional features. In this study, we optimized shape and size of scaffolds for bio-root regeneration using computer aided design (CAD) modeling and finite element analysis (FEA). Statical structural analysis showed the total deformation (TD) and equivalent von-mises stress (EQV) of the restored tooth model mainly concentrated on the scaffold and the post, in accordance with the condition in a natural post restored tooth. Design sensitivity analysis showed increasing the height and upper diameter of the scaffold can tremendously reduce the TD and EQV of the model, while increasing the bottom diameter of scaffold can, to some extent, reduce the EQV in post. However, increase on post height had little influence on the whole model, only slightly increased the native EQV stress in post. Through response surface based optimization, we successfully screened out the optimal shape of the scaffold used in tissue engineering of tooth root. The optimal scaffold adopted a slightly tapered shape with the upper diameter of 4.9 mm, bottom diameter of 3.4 mm; the length of the optimized scaffold shape was 9.4 mm. While the analysis also suggested a height of about 9 mm for a metal post with a diameter of 1.4 mm suitable for crown restoration in bio-root regeneration. In order to validate the physiological function of the shape optimized scaffold in vivo, we transplanted the shape optimized treated dentin matrix (TDM) scaffold, seeding with dental stem cells, into alveolar bone of swine and further installed porcelain crown. Results showed that tooth root has not only been successfully regenerated histologically but also performed masticatory function and maintained stable for three months after crown restoration. Our results suggested that TDM scaffold with 9.4 mm in length and 4.9 mm/3.4 mm in upper/bottom diameter is a suitable biological scaffold for tooth root regeneration. These results also provided a recommendable design protocol for fabricating other scaffolds in tooth root reconstruction. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Biomaterials 07/2015; 57. DOI:10.1016/j.biomaterials.2015.03.062 · 8.56 Impact Factor
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    • "All rights reserved. dental follicle precursor cells (Miura et al., 2003; Seo et al., 2004; Sonoyama et al., 2006). These post-natal populations have MSC-like features, namely the capacity for self-renewal and the potential to differentiate into multiple lineages including osteoblasts and chondroblasts (Huang et al., 2009). "
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    ABSTRACT: In recent years, human dental pulp stromal cells (DPSCs) have received growing attention due to their characteristics in common with other mesenchymal stem cells, in addition to the ease with which they can be harvested. In this study, we demonstrated that the isolation of DPSCs from third molar teeth of healthy individuals allowed the recovery of dental mesenchymal stem cells that showed self-renewal and multipotent differentiation capability. DPSCs resulted positive for CD73, CD90, CD105, STRO-1, negative for CD34, CD45, CD14 and were able to differentiate into osteogenic and chondrogenic cells. We also assayed the angiogenic potential of DPSCs, their capillary tube-like formation was assessed using an in vitro angiogenesis assay and the uptake of acetylated low-density lipoprotein was measured as a marker of endothelial function. Based on these results, DPSCs were capable of differentiating into cells with phenotypic and functional features of endothelial cells. Furthermore, this study investigated the growth and differentiation of human DPSCs under a variety of bioengineering platforms, such as low frequency ultrasounds, tissue engineering and nanomaterials. DPSCs showed an enhanced chondrogenic differentiation under ultrasound application. Moreover, DPSCs were tested on different scaffolds, poly(vinyl alcohol)/gelatin (PVA/G) sponges and human plasma clots. We showed that both PVA/G and human plasma clot are suitable scaffolds for adhesion, growth and differentiation of DPSCs toward osteoblastic lineages. Finally, we evaluated the interactions of DPSCs with a novel class of nanomaterials, namely boron nitride nanotubes (BNNTs). From our investigation, DPSCs have appeared as a highly versatile cellular tool to be employed in regenerative medicine.
    Micron 12/2014; 67:155–168. DOI:10.1016/j.micron.2014.07.003 · 1.99 Impact Factor
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