·
REVIEW
·

Oral stem cells, decoding and mapping the resident cells populations

Xuechen Zhang1 ,  Ana Justo Caetano1 ,  Paul T. Sharpe1,2* ,  Ana Angelova Volponi1*
Show Less
1 Centre for Craniofacial and Regenerative Biology, Faculty of Dentistry, Oral & Craniofacial Sciences, King’s College University of London, London, UK
2 Laboratory of Odontogenesis and Osteogenesis, Institute of Animal Physiology and Genetics, CAS, v.v.i., Brno, Czech Republic
BMT 2022 , 3(1), 24–30; https://doi.org/10.12336/biomatertransl.2022.01.004
Submitted: 11 December 2021 | Revised: 9 March 2022 | Accepted: 12 March 2022 | Published: 28 March 2022
Copyright © 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
Download PDF
Cite
XML
Abstract

The teeth and their supporting tissues provide an easily accessible source of oral stem cells. These different stem cell populations have been extensively studied for their properties, such as high plasticity and clonogenicity, expressing stem cell markers and potency for multilineage differentiation in vitro. Such cells with stem cell properties have been derived and characterised from the dental pulp tissue, the apical papilla region of roots in development, as well as the supporting tissue of periodontal ligament that anchors the tooth within the alveolar socket and the soft gingival tissue. Studying the dental pulp stem cell populations in a continuously growing mouse incisor model, as a traceable in vivo model, enables the researchers to study the properties, origin and behaviour of mesenchymal stem cells. On the other side, the oral mucosa with its remarkable scarless wound healing phenotype, offers a model to study a well-coordinated system of healing because of coordinated actions between epithelial, mesenchymal and immune cells populations. Although described as homogeneous cell populations following their in vitro expansion, the increasing application of approaches that allow tracing of individual cells over time, along with single-cell RNA-sequencing, reveal that different oral stem cells are indeed diverse populations and there is a highly organised map of cell populations according to their location in resident tissues, elucidating diverse stem cell niches within the oral tissues. This review covers the current knowledge of diverse oral stem cells, focusing on the new approaches in studying these cells. These approaches “decode” and “map” the resident cells populations of diverse oral tissues and contribute to a better understanding of the “stem cells niche architecture and interactions. Considering the high accessibility and simplicity in obtaining these diverse stem cells, the new findings offer potential in development of translational tissue engineering approaches and innovative therapeutic solutions.

Keywords
dental pulp stem cells
dental stem cells
gingival stem cells
periodontal ligament stem cells
stem cells from apical papilla
References

Below is the content of the Citations in the paper which has been de-formatted, however, the content stays consistent with the original.

1. Nanci, A. Ten Cate’s oral histology: development, structure, and function. 8th ed.; Elsevier: St. Louis, 2012.  
2. Gronthos, S.; Mankani, M.; Brahim, J.; Robey, P. G.; Shi, S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci U S A. 2000, 97, 13625-13630.  
3. Gronthos, S.; Brahim, J.; Li, W.; Fisher, L. W.; Cherman, N.; Boyde, A.; DenBesten, P.; Robey, P. G.; Shi, S. Stem cell properties of human dental pulp stem cells. J Dent Res. 2002, 81, 531-535.  
4. Jo, Y. Y.; Lee, H. J.; Kook, S. Y.; Choung, H. W.; Park, J. Y.; Chung, J. H.; Choung, Y. H.; Kim, E. S.; Yang, H. C.; Choung, P. H. Isolation and characterization of postnatal stem cells from human dental tissues. Tissue Eng. 2007, 13, 767-773.  
5. Huang, G. T.; Gronthos, S.; Shi, S. Mesenchymal stem cells derived from dental tissues vs. those from other sources: their biology and role in regenerative medicine. J Dent Res. 2009, 88, 792-806.  
6. Balic, A.; Aguila, H. L.; Caimano, M. J.; Francone, V. P.; Mina, M. Characterization of stem and progenitor cells in the dental pulp of erupted and unerupted murine molars. Bone. 2010, 46, 1639-1651.  
7. Volponi, A. A.; Pang, Y.; Sharpe, P. T. Stem cell-based biological tooth repair and regeneration. Trends Cell Biol. 2010, 20, 715-722.  
8. Volponi, A. A.; Sharpe, P. T. The tooth -- a treasure chest of stem cells. Br Dent J. 2013, 215, 353-358.  
9. Angelova Volponi, A.; Zaugg, L. K.; Neves, V.; Liu, Y.; Sharpe, P. T. Tooth repair and regeneration. Curr Oral Health Rep. 2018, 5, 295-303.  
10. Yelick, P. C.; Sharpe, P. T. Tooth bioengineering and regenerative dentistry. J Dent Res. 2019, 98, 1173-1182.  
11. Smith, A. J.; Lesot, H. Induction and regulation of crown dentinogenesis: embryonic events as a template for dental tissue repair? Crit Rev Oral Biol Med. 2001, 12, 425-437.  
12. Smith, J. G.; Smith, A. J.; Shelton, R. M.; Cooper, P. R. Recruitment of dental pulp cells by dentine and pulp extracellular matrix components. Exp Cell Res. 2012, 318, 2397-2406.  
13. Smith, A. J.; Cassidy, N.; Perry, H.; Bègue-Kirn, C.; Ruch, J. V.; Lesot, H. Reactionary dentinogenesis. Int J Dev Biol. 1995, 39, 273-280.  
14. Couve, E.; Osorio, R.; Schmachtenberg, O. Reactionary dentinogenesis and neuroimmune response in dental caries. J Dent Res. 2014, 93, 788-793.  
15. Teaford, M. F.; Smith, M. M.; Ferguson, M. W. J. Development, function and evolution of teeth. Cambridge University Press: Cambridge, 2000.  
16. Feng, J.; Mantesso, A.; De Bari, C.; Nishiyama, A.; Sharpe, P. T. Dual origin of mesenchymal stem cells contributing to organ growth and repair. Proc Natl Acad Sci U S A. 2011, 108, 6503-6508.  
17. Vidovic, I.; Banerjee, A.; Fatahi, R.; Matthews, B. G.; Dyment, N. A.; Kalajzic, I.; Mina, M. αSMA-expressing perivascular cells represent dental pulp progenitors in vivo. J Dent Res. 2017, 96, 323-330.  
18. Kaukua, N.; Shahidi, M. K.; Konstantinidou, C.; Dyachuk, V.; Kaucka, M.; Furlan, A.; An, Z.; Wang, L.; Hultman, I.; Ahrlund-Richter, L.; Blom, H.; Brismar, H.; Lopes, N. A.; Pachnis, V.; Suter, U.; Clevers, H.; Thesleff, I.; Sharpe, P.; Ernfors, P.; Fried, K.; Adameyko, I. Glial origin of mesenchymal stem cells in a tooth model system. Nature. 2014, 513, 551-554.  
19. Miura, M.; Gronthos, S.; Zhao, M.; Lu, B.; Fisher, L. W.; Robey, P. G.; Shi, S. SHED: stem cells from human exfoliated deciduous teeth. Proc Natl Acad Sci U S A. 2003, 100, 5807-5812.  
20. Shi, S.; Bartold, P. M.; Miura, M.; Seo, B. M.; Robey, P. G.; Gronthos, S. The efficacy of mesenchymal stem cells to regenerate and repair dental structures. Orthod Craniofac Res. 2005, 8, 191-199.  
21. Sakai, V. T.; Zhang, Z.; Dong, Z.; Neiva, K. G.; Machado, M. A.; Shi, S.; Santos, C. F.; Nör, J. E. SHED differentiate into functional odontoblasts and endothelium. J Dent Res. 2010, 89, 791-796.  
22. Cordeiro, M. M.; Dong, Z.; Kaneko, T.; Zhang, Z.; Miyazawa, M.; Shi, S.; Smith, A. J.; Nör, J. E. Dental pulp tissue engineering with stem cells from exfoliated deciduous teeth. J Endod. 2008, 34, 962-969.  
23. Wang, J.; Wang, X.; Sun, Z.; Wang, X.; Yang, H.; Shi, S.; Wang, S. Stem cells from human-exfoliated deciduous teeth can differentiate into dopaminergic neuron-like cells. Stem Cells Dev. 2010, 19, 1375-1383.  
24. Nakamura, S.; Yamada, Y.; Katagiri, W.; Sugito, T.; Ito, K.; Ueda, M. Stem cell proliferation pathways comparison between human exfoliated deciduous teeth and dental pulp stem cells by gene expression profile from promising dental pulp. J Endod. 2009, 35, 1536-1542.  
25. Laing, A. G.; Fanelli, G.; Ramirez-Valdez, A.; Lechler, R. I.; Lombardi, G.; Sharpe, P. T. Mesenchymal stem cells inhibit T-cell function through conserved induction of cellular stress. PLoS One. 2019, 14, e0213170.  
26. Laing, A. G.; Riffo-Vasquez, Y.; Sharif-Paghaleh, E.; Lombardi, G.; Sharpe, P. T. Immune modulation by apoptotic dental pulp stem cells in vivo. Immunotherapy. 2018, 10, 201-211.  
27. Gazarian, K. G.; Ramírez-García, L. R. Human deciduous teeth stem cells (SHED) display neural crest signature characters. PLoS One. 2017, 12, e0170321.  
28. Huang, G. T.; Sonoyama, W.; Liu, Y.; Liu, H.; Wang, S.; Shi, S. The hidden treasure in apical papilla: the potential role in pulp/dentin regeneration and bioroot engineering. J Endod. 2008, 34, 645-651.  
29. Sonoyama, W.; Liu, Y.; Yamaza, T.; Tuan, R. S.; Wang, S.; Shi, S.; Huang, G. T. Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. J Endod. 2008, 34, 166-171.  
30. Hilkens, P.; Bronckaers, A.; Ratajczak, J.; Gervois, P.; Wolfs, E.; Lambrichts, I. The angiogenic potential of DPSCs and SCAPs in an in vivo model of dental pulp regeneration. Stem Cells Int. 2017, 2017, 2582080.  
31. Liu, C.; Xiong, H.; Chen, K.; Huang, Y.; Huang, Y.; Yin, X. Long-term exposure to pro-inflammatory cytokines inhibits the osteogenic/dentinogenic differentiation of stem cells from the apical papilla. Int Endod J. 2016, 49, 950-959.  
32. Chen, H.; Fu, H.; Wu, X.; Duan, Y.; Zhang, S.; Hu, H.; Liao, Y.; Wang, T.; Yang, Y.; Chen, G.; Li, Z.; Tian, W. Regeneration of pulpo-dentinal-like complex by a group of unique multipotent CD24a(+) stem cells. Sci Adv. 2020, 6, eaay1514.  
33. Nada, O. A.; El Backly, R. M. Stem cells from the apical papilla (SCAP) as a tool for endogenous tissue regeneration. Front Bioeng Biotechnol. 2018, 6, 103.  
34. Jeon, B. G.; Kang, E. J.; Kumar, B. M.; Maeng, G. H.; Ock, S. A.; Kwack, D. O.; Park, B. W.; Rho, G. J. Comparative analysis of telomere length, telomerase and reverse transcriptase activity in human dental stem cells. Cell Transplant. 2011, 20, 1693-1705.  
35. Volponi, A. A.; Gentleman, E.; Fatscher, R.; Pang, Y. W.; Gentleman, M. M.; Sharpe, P. T. Composition of mineral produced by dental mesenchymal stem cells. J Dent Res. 2015, 94, 1568-1574.  
36. Bakopoulou, A.; Kritis, A.; Andreadis, D.; Papachristou, E.; Leyhausen, G.; Koidis, P.; Geurtsen, W.; Tsiftsoglou, A. Angiogenic potential and secretome of human apical papilla mesenchymal stem cells in various stress microenvironments. Stem Cells Dev. 2015, 24, 2496-2512.  
37. Yu, S.; Zhao, Y.; Ma, Y.; Ge, L. Profiling the secretome of human stem cells from dental apical papilla. Stem Cells Dev. 2016, 25, 499-508.  
38. Diogenes, A.; Hargreaves, K. M. Microbial modulation of stem cells and future directions in regenerative endodontics. J Endod. 2017, 43, S95-S101.  
39. Yi, B.; Ding, T.; Jiang, S.; Gong, T.; Chopra, H.; Sha, O.; Dissanayaka, W. L.; Ge, S.; Zhang, C. Conversion of stem cells from apical papilla into endothelial cells by small molecules and growth factors. Stem Cell Res Ther. 2021, 12, 266.  
40. Pereira, D.; Sequeira, I. A scarless healing tale: comparing homeostasis and wound healing of oral mucosa with skin and oesophagus. Front Cell Dev Biol. 2021, 9, 682143.  
41. Lindhe, J.; Lang, N. P.; Karring, T. Clinical periodontology and implant dentistry. 5th ed.; Wiley-Blackwell: 2008.  
42. Zhang, Q.; Shi, S.; Liu, Y.; Uyanne, J.; Shi, Y.; Shi, S.; Le, A. D. Mesenchymal stem cells derived from human gingiva are capable of immunomodulatory functions and ameliorate inflammation-related tissue destruction in experimental colitis. J Immunol. 2009, 183, 7787-7798.  
43. Yang, H.; Gao, L. N.; An, Y.; Hu, C. H.; Jin, F.; Zhou, J.; Jin, Y.; Chen, F. M. Comparison of mesenchymal stem cells derived from gingival tissue and periodontal ligament in different incubation conditions. Biomaterials. 2013, 34, 7033-7047.  
44. Nakamura, T.; Inatomi, T.; Sotozono, C.; Amemiya, T.; Kanamura, N.; Kinoshita, S. Transplantation of cultivated autologous oral mucosal epithelial cells in patients with severe ocular surface disorders. Br J Ophthalmol. 2004, 88, 1280-1284.  
45. Nakamura, T.; Takeda, K.; Inatomi, T.; Sotozono, C.; Kinoshita, S. Long-term results of autologous cultivated oral mucosal epithelial transplantation in the scar phase of severe ocular surface disorders. Br J Ophthalmol. 2011, 95, 942-946.  
46. Nagata, M.; Chu, A. K. Y.; Ono, N.; Welch, J. D.; Ono, W. Single-cell transcriptomic analysis reveals developmental relationships and specific markers of mouse periodontium cellular subsets. Front Dent Med. 2021, 2, 679937.  
47. Wada, N.; Menicanin, D.; Shi, S.; Bartold, P. M.; Gronthos, S. Immunomodulatory properties of human periodontal ligament stem cells. J Cell Physiol. 2009, 219, 667-676.  
48. Zhao, J.; Volponi, A. A.; Caetano, A.; Sharpe, P. T. Mesenchymal stem cells in teeth. In Encyclopedia of Bone Biology, Elsevier: 2020; pp 109-118.  
49. Iwasaki, K.; Komaki, M.; Yokoyama, N.; Tanaka, Y.; Taki, A.; Kimura, Y.; Takeda, M.; Oda, S.; Izumi, Y.; Morita, I. Periodontal ligament stem cells possess the characteristics of pericytes. J Periodontol. 2013, 84, 1425-1433.  
50. Caetano, A. J.; Yianni, V.; Volponi, A.; Booth, V.; D’Agostino, E. M.; Sharpe, P. Defining human mesenchymal and epithelial heterogeneity in response to oral inflammatory disease. eLife. 2021, 10, e62810.  
51. Human cell atlas. https://www.humancellatlas.org/.Access March 1, 2022.  
52. An, Z.; Sabalic, M.; Bloomquist, R. F.; Fowler, T. E.; Streelman, T.; Sharpe, P. T. A quiescent cell population replenishes mesenchymal stem cells to drive accelerated growth in mouse incisors. Nat Commun. 2018, 9, 378.  
53. An, Z.; Akily, B.; Sabalic, M.; Zong, G.; Chai, Y.; Sharpe, P. T. Regulation of mesenchymal stem to transit-amplifying cell transition in the continuously growing mouse incisor. Cell Rep. 2018, 23, 3102-3111.  
54. Seidel, K.; Marangoni, P.; Tang, C.; Houshmand, B.; Du, W.; Maas, R. L.; Murray, S.; Oldham, M. C.; Klein, O. D. Resolving stem and progenitor cells in the adult mouse incisor through gene co-expression analysis. eLife. 2017, 6, e24712.  
55. Krivanek, J.; Soldatov, R. A.; Kastriti, M. E.; Chontorotzea, T.; Herdina, A. N.; Petersen, J.; Szarowska, B.; Landova, M.; Matejova, V. K.; Holla, L. I.; Kuchler, U.; Zdrilic, I. V.; Vijaykumar, A.; Balic, A.; Marangoni, P.; Klein, O. D.; Neves, V. C. M.; Yianni, V.; Sharpe, P. T.; Harkany, T.; Metscher, B. D.; Bajénoff, M.; Mina, M.; Fried, K.; Kharchenko, P. V.; Adameyko, I. Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth. Nat Commun. 2020, 11, 4816.  
56. Yu, T.; Volponi, A. A.; Babb, R.; An, Z.; Sharpe, P. T. Stem cells in tooth development, growth, repair, and regeneration. Curr Top Dev Biol. 2015, 115, 187-212.  
57. Zhao, J.; Faure, L.; Adameyko, I.; Sharpe, P. T. Stem cell contributions to cementoblast differentiation in healthy periodontal ligament and periodontitis. Stem Cells. 2021, 39, 92-102.  

Conflict of interest
The authors declare they have no competing interests.
Share
Back to top
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept