Dental Follicle Cells
Where teeth stem from
Credit: Art by Alexandra Banbanaste. Set in motion by Dr. Emanuele Petretto. Words by Semeli Platsaki, PhD. Project Coordinator: Dr. Masia Maksymowicz. Series Director: Dr. Radhika Patnala
#Extraordinarycelltypes #sciart #lifescience
To look a gift rat in the mouth
Ah the dental follicle! Where teeth stem from, where the magic happens! Hang on, there’s also something to do with rats! Let’s start from the top. Dental Follicle Cells (DFCs) were first isolated from rat molars and are behind the continuous growth of rodent incisors (1, 2). DFCs are a unique population of mesenchymal stem cells residing in the dental follicle (1), the protective envelope surrounding the dental papilla and the enamel-producing organ. All together, these form what is called the tooth germ, the precursor of a fully developed tooth. Originating from the cranial neural crest, the dental follicle tissue and DFCs have a central role in odontogenesis (tooth formation). DFCs give rise to the periodontium tissue including the cementum, the alveolar bone and the periodontal ligament (3).
Full of potential
True to form, DFCs have the main features of classic stem cells, meaning the capacity to self-renew and differentiate (1). DFCs express a variety of cell surface markers, indicating the intrinsic variety of cell populations they can develop into (including mesenchymal cell markers, neural crest stem cell markers, and glial-like cell markers). In addition, they strongly express NOTCH-1, a transmembrane protein that is crucial for cell fate decisions (3). Their differentiation potential is illustrated by the range of cells DFCs differentiate into, including cementoblasts, chondrocytes, adipocytes (4, 5), osteoblasts (6) and even neural-like cells (7, 8). Several signaling pathways instruct the different stages of tooth development, such as tooth eruption and morphogenesis. illustrating the complexity of tooth formation. This multistep process requires careful coordination, in which DFCs play a central role.
To tooth formation and beyond
DFCs are involved in tooth formation through two differentiation routes. The osteogenic differentiation of DFCs leads to the formation of osteoblasts (3, 9, 10), cells that are involved in bone synthesis and mineral matrix formation. Through osteogenic differentiation DFCs contribute to the formation of the alveolar bone, responsible for supporting the tooth root. The signaling pathways involved in bone formation include NOTCH, Hedgehog, BMPs, and WNT (necessary for epithelial-mesenchymal interactions that are important for bone formation). Another route of DFC differentiation, periodontium differentiation, is responsible for the creation of a strong root-bone interface, which comes hand in hand with the formation of the periodontal ligament, cementum and alveolar bone (3). During this stage, DFCs form cementoblasts that produce cementum, the mineralized layer protecting the tooth root and mediating the interactions between the root and the periodontal ligament.
Taking an unexpected twist from tooth development, DFCs can also differentiate into other cell types. Thanks to the neural crest origin of DFCs, they are able to differentiate into functional neurons. Neural crest cells tend to migrate to different parts of the body where they contribute to tissue development of different organs (4). In the case of tooth formation, some neural crest cells remain undifferentiated. Finally, another example of cells that DFCs can turn into are adipocytes, cells with endocrine and energy storage functions. For that DFCs require to be cultured in the right medium and with tight control of calcium concentration, to inhibit their differentiation towards the osteogenic direction (11).
Regenerative medicine, here we come!
The features described above portray DFCs as multipotent cell magicians and promising candidates for regenerative medicine and tissue engineering. The human dental follicle is an excellent source of neural stem cells in the perspective of regenerative therapy (4). DFCs are particularly interesting as they can be ethically sourced in a non-invasive manner from completely damaged third molars, which are considered to be dental waste (4, 12). Potential future applications of DFCs, taking advantage of their osteogenic potential, include bone regeneration and transplantation therapy in cases of bone loss due to periodontitis (4, 9).
On the other hand, their neurogenic potential means they are promising targets for cell therapy development against neurodegenerative disease (4). Interestingly, DFCs have been reported to differentiate into dopaminergic neurons, highlighting them as therapeutic candidates for treating Parkinson’s disease (13). In particular, they have been shown to successfully differentiate into dopaminergic neurons when transplanted into a mouse model of Parkinson’s disease, contributing to the maintenance of partially damaged neurons (13). Altogether, DFCs present a promising lead for the future of cell-based regenerative medicine, one that is definitely worth keeping an eye on.
Recognizing and appreciating the labs working in this space:
- Shaomian Yao group, Department of Comparative Biomedical Sciences, LSU School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803 https://www.lsu.edu/vetmed/faculty/yao.php
- Ono & Ono Laboratory, UTHealth School of Dentistry Research Labs, Houston, Texas,https://dentistry.uth.edu/research/labs/sod-lab?id=e811089b-2c1c-4054-a6eb-2cc7e10f5a8a, Twitter: https://x.com/UTSDhouston, Instagram: https://www.instagram.com/utsdhouston/
- Pamela Yelick Lab, Department of Orthodontics, Division of Craniofacial and Molecular Genetics, Tufts University School of Dental Medicine, Boston, MA, United States. https://facultyprofiles.tufts.edu/pamela-yelick
- William Giannobile Lab, Department of Oral Medicine, Infection, and Immunity, Harvard School of Dental Medicine, Boston, MA, United States. https://hsdm.harvard.edu/giannobile-laboratory
- Yi Fan Group, National Clinical Research Center for Oral Diseases, State Key Laboratory of Oral Diseases, Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
- Yongwen Guo Group, State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Orthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
- Thomas Diekwisch Lab, Department of Orthodontics and Oral Biology, Brodie Laboratory for Craniofacial Genetics, The University of Illinois at Chicago College of Dentistry, Chicago, IL 60612, USA. https://dentistry.tamu.edu/departments/periodontics/faculty/thomas-diekwisch.html
- Nör Lab, Department of Cariology, Restorative Sciences, and Endodontics, University of Michigan School of Dentistry, Ann Arbor, Michigan 48109–1078, USA. https://media.dent.umich.edu/labs/nor/
References
- Bi, Ruiye et al. “Function of Dental Follicle Progenitor/Stem Cells and Their Potential in Regenerative Medicine: From Mechanisms to Applications.” Biomolecules vol. 11,7 997. 7 Jul. 2021, doi:10.3390/biom11070997
- He, Mengting et al. “Rodent incisor and molar dental follicles show distinct characteristics in tooth eruption.” Archives of oral biology vol. 126 (2021): 105117. doi:10.1016/j.archoralbio.2021.105117
- Zhou, Tao et al. “Dental Follicle Cells: Roles in Development and Beyond.” Stem cells international vol. 2019 9159605. 15 Sep. 2019, doi:10.1155/2019/9159605
- Lima, Rodrigo Lopes et al. “Human dental follicle cells express embryonic, mesenchymal and neural stem cells markers.” Archives of oral biology vol. 73 (2017): 121–128. doi:10.1016/j.archoralbio.2016.10.003
- Kémoun, Philippe et al. “Human dental follicle cells acquire cementoblast features under stimulation by BMP-2/-7 and enamel matrix derivatives (EMD) in vitro.” Cell and tissue research vol. 329,2 (2007): 283–94. doi:10.1007/s00441–007–0397–3
- Morsczeck, C et al. “Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth.” Matrix biology : journal of the International Society for Matrix Biology vol. 24,2 (2005): 155–65. doi:10.1016/j.matbio.2004.12.004
- Völlner, Florian et al. “A two-step strategy for neuronal differentiation in vitro of human dental follicle cells.” Differentiation; research in biological diversity vol. 77,5 (2009): 433–41. doi:10.1016/j.diff.2009.03.002
- Ernst, Wolfgang et al. “Comparison of murine dental follicle precursor and retinal progenitor cells after neural differentiation in vitro.” Cell biology international vol. 33,7 (2009): 758–64. doi:10.1016/j.cellbi.2009.04.005
- Mori, Giorgio et al. “Osteogenic differentiation of dental follicle stem cells.” International journal of medical sciences vol. 9,6 (2012): 480–7. doi:10.7150/ijms.4583
- Morsczeck, C. “Gene expression of runx2, Osterix, c-fos, DLX-3, DLX-5, and MSX-2 in dental follicle cells during osteogenic differentiation in vitro.” Calcified tissue international vol. 78,2 (2006): 98–102. doi:10.1007/s00223–005–0146–0
- Nelson, Piper et al. “Transient receptor potential melastatin 4 channel controls calcium signals and dental follicle stem cell differentiation.” Stem cells (Dayton, Ohio) vol. 31,1 (2013): 167–77. doi:10.1002/stem.1264
- Ikeda, Etsuko et al. “Osteogenic differentiation of human dental papilla mesenchymal cells.” Biochemical and biophysical research communications vol. 342,4 (2006): 1257–62. doi:10.1016/j.bbrc.2006.02.101
- Bi, Fei et al. “Dental follicle cells show potential for treating Parkinson’s disease through dopaminergic-neuronogenic differentiation.” Human cell vol. 35,6 (2022): 1708–1721. doi:10.1007/s13577–022–00774–6
About the author:
DR. SEMELI PLATSAKI
Content Editor The League of Extraordinary Cell Types, Sci-Illustrate Stories
Semeli is a biochemist at heart, holding a degree in Chemistry and a PhD in protein biochemistry. After working as a researcher studying the structure-function relationship of protein in a range of biological contexts, from bacterial metalloproteins to synaptic signaling, Semeli moved on to a role in Scientific communication and project management in the European Virus Archive, a collection of virus and virus-derived resources available to researchers worldwide. Semeli is passionate about the creative mix of art, words and science, one of the best ways to make Science impactful.
About the artist:
ALEXANDRA BANBANASTE
Contributing Artist The League of Extraordinary Cell Types, Sci-Illustrate Stories
Alexandra Banbanaste is completing her Master’s in Chemical Engineering at Ecole Polytechnique Fédérale de Lausanne, where she studied neuroscience, chemistry, and biology.
Apart from being a passionate scientist, she also helps industries and scientists better communicate complex scientific ideas. Her work includes research on small kinase inhibitors at Origenis GmbH and on polymer additives characterization at the Laboratory of Macromolecules and Organic Materials. Currently, she is completing her Master’s thesis in protein design at the Laboratory of Biomolecular Modeling, and plans to continue her academic journey by pursuing a PhD in drug design.
About the animator:
DR. EMANUELE PETRETTO
Animator The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behavior of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.
Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualization, motion design, and games, he wants to show the wonders of the complexity surrounding us.
About the series:
The League of Extraordinary Cell types
The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types in our body, that make our hearts tick ❤.
