Dental-derived Stem Cells and whole Tooth Regeneration: an Overview

With increasing life expectancy, demands for dental tissue and whole-tooth regeneration are becoming more significant. Despite great progress in medicine, including regenerative therapies, the complex structure of dental tissues introduces several challenges to the field of regenerative dentistry. Interdisciplinary efforts from cellular biologists, material scientists, and clinical odontologists are being made to establish strategies and find the solutions for dental tissue regeneration and/or whole-tooth regeneration. In recent years, many significant discoveries were done regarding signaling pathways and factors shaping calcified tissue genesis, including those of tooth. Novel biocompatible scaffolds and polymer-based drug release systems are under development and may soon result in clinically applicable biomaterials with the potential to modulate signaling cascades involved in dental tissue genesis and regeneration. Approaches for whole-tooth regeneration utilizing adult stem cells, induced pluripotent stem cells, or tooth germ cells transplantation are emerging as promising alternatives to overcome existing in vitro tissue generation hurdles. In this interdisciplinary review, most recent advances in cellular signaling guiding dental tissue genesis, novel functionalized scaffolds and drug release material, various odontogenic cell sources, and methods for tooth regeneration are discussed thus providing a multi-faceted, up-to-date, and illustrative overview on the tooth regeneration matter, alongside hints for future directions in the challenging field of regenerative dentistry.

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Stem Cells in the Face: Tooth Regeneration and Beyond

Cell Stem Cell ◽

10.1016/j.stem.2012.08.010 ◽

2012 ◽

Vol 11 (3) ◽

pp. 291-301 ◽

Cited By ~ 73

Author(s):

Jeremy J. Mao ◽

Darwin J. Prockop

Keyword(s):

Stem Cells ◽

Tooth Regeneration ◽

The Face

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Regeneration of pulpo-dentinal–like complex by a group of unique multipotent CD24a+ stem cells

Science Advances ◽

10.1126/sciadv.aay1514 ◽

2020 ◽

Vol 6 (15) ◽

pp. eaay1514 ◽

Cited By ~ 4

Author(s):

Hong Chen ◽

Huancheng Fu ◽

Xue Wu ◽

Yufeng Duan ◽

Sicheng Zhang ◽

...

Keyword(s):

Stem Cells ◽

Dental Pulp ◽

Three Dimensional ◽

Transcriptional Factor ◽

Tooth Regeneration ◽

Spheroid Culture ◽

Multipotent Stem Cells ◽

Dental Papilla ◽

Bona Fide

Dental pulp is critical to maintain the vitality of a tooth. Regeneration of pulpo-dentinal complex is of great interest to treat pulpitis and pulp necrosis. In this study, through three-dimensional spheroid culture, a group of unique multipotent stem cells were identified from mouse dental papilla called multipotent dental pulp regenerative stem cells (MDPSCs). MDPSCs exhibited enhanced osteogenic/odontogenic differentiation capabilities and could form regenerative dentin and neurovascular-like structures that mimicked the native teeth in vivo. Further analysis revealed that CD24a was the bona fide marker for MDPSCs, and their expansion was highly dependent on the expression of a key transcriptional factor, Sp7. Last, CD24a+ cells could be detected in primary dental papilla in mice and human, suggesting that MDPSCs resided in their native niches. Together, our study has identified a previously unidentified group of multipotent pulp regenerative stem cells with defined molecular markers for the potential treatment of pulpitis and pulp necrosis.

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Regenerative Applications Using Tooth Derived Stem Cells in Other Than Tooth Regeneration: A Literature Review

Stem Cells International ◽

10.1155/2016/9305986 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 31

Author(s):

Yun-Jong Park ◽

Seunghee Cha ◽

Young-Seok Park

Keyword(s):

Stem Cells ◽

Stromal Cells ◽

Bone Marrow Stromal Cells ◽

Marrow Stromal Cells ◽

Tooth Regeneration ◽

Future Perspectives ◽

Dental Stem Cells ◽

Original Function ◽

Tooth Structure ◽

Promising Source

Tooth derived stem cells or dental stem cells are categorized according to the location from which they are isolated and represent a promising source of cells for regenerative medicine. Originally, as one kind of mesenchymal stem cells, they are considered an alternative of bone marrow stromal cells. They share many commonalties but maintain differences. Considering their original function in development and the homeostasis of tooth structures, many applications of these cells in dentistry have aimed at tooth structure regeneration; however, the application in other than tooth structures has been attempted extensively. The availability from discarded or removed teeth can be an innate benefit as a source of autologous cells. Their origin from the neural crest results in exploitation of neurological and numerous other applications. This review briefly highlights current and future perspectives of the regenerative applications of tooth derived stem cells in areas beyond tooth regeneration.

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Review scaffold design and stem cells for tooth regeneration

Japanese Dental Science Review ◽

10.1016/j.jdsr.2012.09.001 ◽

2013 ◽

Vol 49 (1) ◽

pp. 14-26 ◽

Cited By ~ 46

Author(s):

Li Zhang ◽

Yosry Morsi ◽

Yanying Wang ◽

Yubao Li ◽

Seeram Ramakrishna

Keyword(s):

Stem Cells ◽

Tooth Regeneration ◽

Scaffold Design

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Stem cells: potential implications for tooth regeneration and tissue engineering in craniofacial defects

International Journal of Oral and Maxillofacial Surgery ◽

10.1016/j.ijom.2009.03.459 ◽

2009 ◽

Vol 38 (5) ◽

pp. 526

Author(s):

M.K. Gupta ◽

M. Nair ◽

S.S. Sandhu

Keyword(s):

Tissue Engineering ◽

Stem Cells ◽

Tooth Regeneration ◽

Craniofacial Defects

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TOOTH REGENERATION WITH DENTAL STEM CELL RESEARCH IN MINIATURE PIG MODEL

Taiwan Veterinary Journal ◽

10.1142/s1682648515500109 ◽

2015 ◽

Vol 41 (03) ◽

pp. 197-203

Author(s):

Tzong-Fu Kuo ◽

Shi-Yuan Sheu ◽

Ching-Chuan Jiang ◽

Hao-Hueng Chang ◽

Shuo-Tsung Chen ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Type I ◽

Tooth Regeneration ◽

Tooth Crown ◽

Dental Stem Cells ◽

Posterior Teeth ◽

Anterior Teeth ◽

Tooth Buds ◽

Mini Pigs

To develop a cell-based approach to tooth regeneration, we isolated dental stem cells from tooth buds of mini pigs and culture-expanded them for about three weeks. Flow cytometry revealed that the majority of the proliferating cells were positive for stem cell surface markers, including CD105, CD29, CD44, CD71. These dental stem cells were then seeded in biodegradable agarose gel for autograft in various areas of the jaw bone. Mini pigs with tooth buds removed without transplantation of dental stem cells served as control. After one year, well differentiated tooth crown and root sheath were formed in mini pigs in the experimental group. The tooth formed by dental stem cells transplanted in alveolar bone was similar in size to original tooth crown (approximately 2 cm × 2 cm × 2 cm). The teeth formed by dental stem cells transplanted under the roots of the anterior teeth and in the cortical bone area were smaller. In the control group, the space where the tooth bud was extracted without cell transplantation was seen to be closed by forward movement of the posterior teeth. Histological analysis showed the structures of enamel, dentin and pulp in the regenerated tooth crown. Immunohistochemical analysis of amelogenin, type I collagen and bone sialoprotein confirmed enamel and dentin formation. Enamel and dentin structures on the regenerated tooth were also identified using scanning electron microscopy. These findings demonstrate a successful model of tooth regeneration from dental stem cells in mini pigs. In addition, local environment and available space also significantly affect the extent of tissue regeneration. Our study demonstrates the feasibility of using dental stem cells for tooth regeneration in clinical applications.

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