Root canal treatments presently offer the most effective treatment for dental infection. However, for decades, endodontists and researchers have recognized the limitations of conventional therapy and searched for novel, biologically based approaches rooted in regenerative medicine.
Researchers at the ADA Forsyth Institute have identified, for the first time, a population of dental pulp stem cells (DPSCs) that originate at the bottom tip of the tooth, known as the apex. The apical stem cells and their regenerative potential contribute toward advanced strategies for regenerative endodontic treatment.
The researchers, including lead author Shinichiro Yoshida, Ph.D., and ADA Forsyth principal investigators Prof. Wei Hsu, Ph.D., and Prof. Takamitsu Maruyama, Ph.D., detailed their findings in “Identification of Apically Localized Endogenous Dental Pulp Stem Cells” in the Journal of Dental Research.
Other collaborators included ADA Forsyth Staff Scientist Eri Maruyama, Ph.D., and George Huang, Ph.D., of the University of Tennessee Health Science Center.
By combining cutting-edge single-cell RNA sequencing with stem cell tracing and transplantation of DPSCs into an ectopic site in an animal model, the researchers showed the ability of this stem cell population to specifically regenerate dental pulp. Dental pulp, soft living tissue located in the center of the tooth, contains blood cells, nerves, and connective tissue. It is crucial for maintaining tooth vitality and function.
“These endogenous stem cells demonstrate self-renewal and production of dental pulp cells,” said ADA Forsyth Assistant Professor Takamitsu Maruyama. “By learning how to guide and control these cells, we may unlock new regenerative therapies to repair teeth damaged by injury or disease.”
Over a period of nine months, researchers observed that this DPSC population gradually expands up the root canal and differentiates into dental pulp cells. They further mature into odontoblasts – the cells that form and maintain dentin.
The researchers also tested the response of the DPSCs to various states of tooth injury. When the pulp is exposed or injured, these newly discovered stem cells quickly multiply and rush to the damaged site, regenerating new pulp tissue and forming a protective layer of dentin that seals the opening of the tooth.
Dr. Maruyama looks forward to studying apically located DPSCs in situations that more closely mirror real dental conditions, testing how they react when the pulp is not just damaged, but also infected — as is often the case in patients.
“Infection might affect the stem cell,” Dr. Maruyama said. “Does it destroy these stem cells, or just silence their power to heal? The more we uncover about how these cells act and what controls them, the closer we get to creating regenerative treatments that can truly maintain live human tooth.”
Regenerative endodontic treatment (RET), including pulp revascularization or pulp revitalization, is an emerging treatment technique, though it is not presently a mainstream option for adult patients. Pulp revascularization has been successfully performed on immature teeth. The American Association of Endodontists has identified regenerative procedures as “one of the most exciting developments in dentistry today” and published clinical guidelines on regenerative therapies.
Pictured: Dental pulp stem cells (marked in red) rapidly expand and migrate toward an injury site.
