What Is It & Why Is It Important

The topic of stem cell and stem cell therapy has become more and more popular in recent years, and for good reason. Researchers are studying stem cells to further our understanding of how diseases occur, as well as how to generate healthy cells that can replace disease affected cells (Mayo Clinic, 2024), also known as regeneration. This included diseases such as diabetes, cancers, heart failure and more (Mayo Clinic, 2024). Similarly to the rest of the body, our oral health can also be benefited through stem cell therapy and understanding.

Stem cell are unique in primarily two general aspects:

• Proliferation: Stem cells have the ability to replicate many times, meaning each stem cell can divide, resulting in more stem cells that can further replicate (NIH, 2021).
• Differentiation: Originally, stem cells are undifferentiated, meaning they do not have any tissue or organ specific characteristics that help them to perform specialized function. However, they have the ability to differentiate, where they can become specialized to gain the characteristics of specific tissue and organs (NIH, 2021).

In essence, this means that if there is an issue in the body, stem cells can be dispatched where they will i) multiply in number and ii) become specialized to aide with the specific situation.

How It Relates To Oral Health

Lets first briefly go over the anatomy of the tooth. starting from the top outside, we have the protective layer of the enamel. This is typically the first line of defense. Working our way in-wards, we have the dentin, pulp and blood vessels (there other parts but lets just use the basics). The enamel acts as the outside shield, with the dentin providing much of the structure and support. Coming from the bottom we have the nerves at both roots of the tooth (the number of roots differs on the tooth, the diagram below has two), where they ultimately combine into the pulp, acting as the heart of the tooth. (The tooth is much more complex than this, but this should do for our purposes). The diagram below should be a great reference for how the various levels are situated

Now, in the tooth, the stem cells are found in the pulp and near the root tips (Sunil et al. 2015). These stem cells found near the root tips (in immature teeth) are called ‘Stem Cells from the Apical Papilla’, otherwise known as SCAP (Weerakoon A. 2018).

Amongst many others, SCAP play the role of repairing and producing new Odontoblasts via differentiation (Liu et al. 2023). Odontoblasts are specialist cells that are responsible for dentin formation, the mineralized tissue which make up the bulk of dental tissue, providing support and protection (Fu & Kim, 2024). Additionally, Odontoblasts also act to transmit information, sending pain signals and pathogen detection so that they can recruit inflammatory mediators and promptly increase dentin formation to protect from bacteria, as well as releasing antimicrobial peptides (Yumoto et al. 2018).

One of the primary controllers of SCAP, and by association Odontoblasts, is Lypoxin A4, otherwise known as LXA4 (Aubeux et al. 2021). LXA4 improves stem cell (both periodontal and SCAP) proliferation, migration and overall healing factors (Aubeux et al. 2021). One of the actions that Odontoblasts do is to, in a nutshell, increase inflammatory reactions in the presence of injury and pathogenic bacteria. While the aim of this is to produce a variety of pro-inflammatory mediators to ultimately initiate innate immune responses, excess inflammation can hurt the host and tooth more than is necessary. Through the binding of LXA4 to the receptors ALX/FPR2, inflammation is regulated, in essence reducing the collateral damage that is caused by immune cells attacking the bacteria (Aubeux et al. 2021). Thus, LXA4 attunes SCAP activity by promoting proliferation, reducing inflammatory products, and directing cell migration response.

Why It Is Important

Understanding how stem cells and their pathways works can drastically alter the future of oral health treatments and procedures. Let take a look at root canal treatments as an example.

When a large cavity has been given time to fester, grow and persist, it will eventually breach the enamel and dentin, reaching the pulp and roots of the infected tooth. As the diagram above depicts, the pulp and roots are full of blood vessels, cells and nerves, all of which will send out distress and pain signals in the presence of cavity bacteria. This is what causes the excruciating throbbing pain and sensitivity of tooth-aches. Even though the body’s cells have immune responses for this scenario, they are only able to mitigate the bacteria to a lower level, typically at a point where the tooth needs to be removed or a root canal treatment is required. In root canal treatments, physical excavation of the site is used in tandem with medicaments to clean out the bacteria, and fill in the damage.

Now, while thankfully root canal treatments are accessible for many, this is still an oral surgery with its own risks, not to mention that it may not be viable for certain situations and severity, as well as being quite costly and long.

This is where stem cells can help with oral recovery. With the use of stem cells like SCAP and their associated ‘partners’ like LXA4, oral tissue regeneration could be a treatment path that may be more beneficial than those currently available. Future dental treatments option may include the use of stem cells to heal oral issues instead of long surgeries and their associated risks. Imagine, where instead of surgeries, our bodies are able to heal themselves from the comfort of your own home without surgery.

To Sum

Stem cell research and how it can help with healthcare treatments is a topic that is continuing to be researched and studied. Stem cells have the ability to self-replicate and specialize into the type of tissue required for healing. With scientific research into oral stem cells like SCAP, the future of oral health prevention and treatment could be radically changed. Hopefully as research progresses into using stem cells, not only for oral health, but for our overall health in general, we will see a paradigm shift, where treatments may become more accessible, quicker, easier and cost-effective.

Stem cells may be the ‘root’ (hehe see what I did there) of a future where every smile can grow to its fullest potential.

References

Aubeux, D., Peters, O. A., Hosseinpour, S., Tessier, S., Geoffroy, V., Pérez, F., & Gaudin, A. (2021). Specialized pro-resolving lipid mediators in Endodontics: A narrative review. BMC Oral Health, 21(1). https://doi.org/10.1186/s12903-021-01619-8

Fu, X., & Kim, H. S. (2024). Dentin Mechanobiology: Bridging the Gap between Architecture and Function. International journal of molecular sciences, 25(11), 5642. https://doi.org/10.3390/ijms25115642

Liu, Q., Gao, Y., & He, J. (2023). Stem Cells from the Apical Papilla (SCAPs): Past, Present, Prospects, and Challenges. Biomedicines, 11(7), 2047. https://doi.org/10.3390/biomedicines11072047

Mayo Clinic Staff. (2024, March 23). Stem cells: What they are and what they do. Mayo Clinic. https://www.mayoclinic.org/tests-procedures/bone-marrow-transplant/in-depth/stem-cells/art-20048117#:~:text=Researchers%20are%20studying%20stem%20cells,how%20diseases%20and%20conditions%20develop.

NIH. (2021, February 1). Stem Cell Basics. National Institutes of Health. https://stemcells.nih.gov/info/basics/stc-basics#:~:text=Stem%20cells%20have%20unique%20abilities,cells%20may%20replicate%20many%20times.

Sunil, P. M., Manikandan, R., Muthumurugan, Yoithapprabhunath, T. R., & Sivakumar, M. (2015). Harvesting dental stem cells – Overview. Journal of pharmacy & bioallied sciences, 7(Suppl 2), S384–S386. https://doi.org/10.4103/0975-7406.163461

Weerakoon, A. (2018, August 28). Using stem cell therapy to repair and regenerate damaged teeth. Dental Words. https://drarosha.com/blog-3/f/stem-cell-therapy-to-repair-and-regenerate-damaged-teeth

Yumoto, H., Hirao, K., Hosokawa, Y., Kuramoto, H., Takegawa, D., Nakanishi, T., & Matsuo, T. (2018). The roles of odontoblasts in dental pulp innate immunity. The Japanese dental science review, 54(3), 105–117. https://doi.org/10.1016/j.jdsr.2018.03.001