Regulation and Differentiation Potential of Dental Mesenchymal Stem Cells

Wang, Lei; Morsczeck, Christian; Gronthos, Stan; Shi, Songtao

doi:10.1002/9781118498026.ch16

Cited by 4 publications

(3 citation statements)

References 70 publications

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“…Most cell therapies prefer the use of autologous cells to avoid transplant rejection, however, MSCs including dental stem cells have a special characteristics-immunosuppression, which can suppress the immune rejection from the host and sustain. [26][27][28] Allogeneic cell source will circumvent problems if autologous cells are not available. Our finding, although preliminary, indicates the possibility that allogeneic DPSCs may be used for pulp regeneration.…”

Section: Discussionmentioning

confidence: 99%

A Miniature Swine Model for Stem Cell-Based De Novo Regeneration of Dental Pulp and Dentin-Like Tissue

Zhu

Liu

et al. 2018

Tissue Engineering Part C: Methods

103

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The goal of this study was to establish mini-swine as a large animal model for stem cell-based pulp regeneration studies. Swine dental pulp stem cells (sDPSCs) were isolated from mini-swine and characterized in vitro. For in vivo studies, we first employed both ectopic and semi-orthotopic study models using severe combined immunodeficiency mice. One is hydroxyapatite-tricalcium phosphate (HA/TCP) model for pulp-dentin complex formation, and the other is tooth fragment model for complete pulp regeneration with new dentin depositing along the canal walls. We found that sDPSCs are similar to their human counterparts exhibiting mesenchymal stem cell characteristics with ability to form colony forming unit-fibroblastic and odontogenic differentiation potential. sDPSCs formed pulp-dentin complex in the HA/TCP model and showed pulp regeneration capacity in the tooth fragment model. We then tested orthotopic pulp regeneration on mini-swine including the use of multi-rooted teeth. Using autologous sDPSCs carried by hydrogel and transplanted into the mini-swine root canal space, we observed regeneration of vascularized pulp-like tissue with a layer of newly deposited dentin-like (rD) tissue or osteodentin along the canal walls. In some cases, dentin bridge-like structure was observed. Immunohistochemical analysis detected the expression of nestin, dentin sialophosphoprotein, dentin matrix protein 1, and bone sialoprotein in odontoblast-like cells lining against the produced rD. We also tested the use of allogeneic sDPSCs for the same procedures. Similar findings were observed in allogeneic transplantation. This study is the first to show an establishment of mini-swine as a suitable large animal model utilizing multi-rooted teeth for further cell-based pulp regeneration studies.

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Section: Discussionmentioning

confidence: 99%

A Miniature Swine Model for Stem Cell-Based De Novo Regeneration of Dental Pulp and Dentin-Like Tissue

Zhu

Liu

et al. 2018

Tissue Engineering Part C: Methods

103

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“…Most cell therapies prefer the use of autologous cells to avoid transplant rejection, as immunosuppression treatment is cumbersome. MSCs, however, have special characteristics-immunosuppression, which can suppress immune rejection from the host and sustain Zhao et al, 2010;Wang et al, 2013). Currently, there is no dental stem cell banking service available.…”

Section: Source Of Stem Cellsmentioning

confidence: 99%

Missing Concepts in De Novo Pulp Regeneration

Huang

Garcı́a-Godoy

2014

J Dent Res

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Regenerative endodontics has gained much attention in the past decade because it offers an alternative approach in treating endodontically involved teeth. Instead of filling the canal space with artificial materials, it attempts to fill the canal with vital tissues. The objective of regeneration is to regain the tissue and restore its function to the original state. In terms of pulp regeneration, a clinical protocol that intends to reestablish pulp/dentin tissues in the canal space has been developed-termed revitalization or revascularization. Histologic studies from animal and human teeth receiving revitalization have shown that pulp regeneration is difficult to achieve. In tissue engineering, there are 2 approaches to regeneration tissues: cell based and cell free. The former involves transplanting exogenous cells into the host, and the latter does not. Revitalization belongs to the latter approach. A number of crucial concepts have not been well discussed, noted, or understood in the field of regenerative endodontics in terms of pulp/dentin regeneration: (1) critical size defect of dentin and pulp, (2) cell lineage commitment to odontoblasts, (3) regeneration vs. repair, and (4) hurdles of cell-based pulp regeneration for clinical applications. This review article elaborates on these missing concepts and analyzes them at their cellular and molecular levels, which will in part explain why the non-cell-based revitalization procedure is difficult to establish pulp/dentin regeneration. Although the cell-based approach has been proven to regenerate pulp/dentin, such an approach will face barriers-with the key hurdle being the shortage of the current good manufacturing practice facilities, discussed herein.

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“…74 The tolerance of transplanted allogeneic DPSCs is likely to be the result of immunosuppressive properties that mesenchymal-type stem/ stromal cells normally possess, which can suppress immune rejection from the host and be sustained. [75][76][77] Despite this observation, a more stringent allogeneic transplantation study should be conducted by examining a long-term tracing of the transplanted cells.…”

Section: Dog Model (Canis Lupus Familiaris)mentioning

confidence: 99%

Animal Models for Stem Cell-Based Pulp Regeneration: Foundation for Human Clinical Applications

Nakashima

Iohara

Bottino

et al. 2019

Tissue Engineering Part B: Reviews

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Rapid progress has been made in the last decade related to stem cell-mediated pulp-dentin regeneration, from characterization of dental pulp stem cells (DPSCs) to the first-ever reported clinical case in humans. However, many challenges still need to be addressed before such technology can become a common clinical practice; therefore, further rigorous research is needed. Animal study models are very important to test new ideas, concepts, and technologies. This review summarizes and discusses several key animal models that have been utilized to investigate pulp-dentin regeneration. From a tissue regeneration perspective, we categorize the animal model by the location where the regenerated pulp tissue is formed: ectopic, semiorthotopic, and orthotopic. Several animal species are discussed, including mouse, ferret, dog, and miniswine. Mouse is used for ectopic pulp-dentin regeneration in the dorsum subcutaneous space. A commonly tested approach is hydroxyapatite/tricalcium phosphate (HA-TCP) granules model used to observe ectopic pulp-dentin complex formation. The semiorthotopic model includes tooth slices or fragments with which de novo pulp regeneration in a root canal space can be tested in the mouse subcutaneous space. For orthotopic pulp regeneration, the canine teeth of ferrets are large enough for such purposes. As nonprimate large animal models, dog and miniswine teeth have many aspects quite similar to those of humans, allowing researchers to perform experiments that mimic clinical conditions in humans. The protocols established and the data obtained from large animal studies may directly relate to and apply to future human studies. Complete orthotopic pulp regeneration has been demonstrated in dogs and miniswine. The use of allogeneic and subpopulations of DPSCs for pulp regeneration, and testing of the periapical disease model and aging model have been performed in miniswine or dogs. In sum, all these animal models will help address challenges that still face pulp regeneration in humans. We need to thoroughly utilize these models to test new ideas, technologies, and strategies before reliable and predictable clinical protocols can be established for human clinical trials or treatment.

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Regulation and Differentiation Potential of Dental Mesenchymal Stem Cells

Cited by 4 publications

References 70 publications

A Miniature Swine Model for Stem Cell-Based De Novo Regeneration of Dental Pulp and Dentin-Like Tissue

A Miniature Swine Model for Stem Cell-Based De Novo Regeneration of Dental Pulp and Dentin-Like Tissue

Missing Concepts in De Novo Pulp Regeneration

Animal Models for Stem Cell-Based Pulp Regeneration: Foundation for Human Clinical Applications

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