February 22, 2019
Long before Hannele Ruohola-Baker became a leading stem cell researcher, she was a young hockey player skating on the frozen ponds of her native Finland. When she was ten years old, she lost a tooth to an errant puck. “I’d say that’s when my interest in regenerating teeth began,” says Dr. Ruohola-Baker, now a Professor of Biochemistry and Associate Director of the UW Medicine Institute for Stem Cell and Regenerative Medicine (ISCRM).
Today, it is common knowledge that adult stem cells are active throughout the human body, helping to maintain organ functioning and regenerate tissue growth after injury. As we age, stem cells begin to regenerate more slowly. This is essentially what getting older means. We break down more often – and recover more slowly.
Many years after her hockey career ended, Dr. Ruohola-Baker and her team at ISCRM set out to investigate the nature of stem cells in teeth. What kinds of stem cells exist in teeth? What are the characteristics of these stem cells? Can the onset of aging be predicted or prevented? And, is it possible to manipulate them for use in actual treatments?
A recent study probing these questions in collaboration with the UW School of Dentistry, is now detailed in a paper published by Scientific Reports (Metabolism as an early predictor of DPSCs aging).
The ISCRM researchers focused their attention on dental pulp stem cells (DPSCs), which are known to repair injured tooth dentin (the dense tissue in teeth found beneath enamel) and which can be affected by aging. Comparing tissue from wisdom teeth donated by more than 300 people through the UW School of Dentistry, Dr. Ruohola-Baker and her team produced several important findings.
First, they were able to identify a pathway (TGF) that is upregulated in DPSCs that age more rapidly. Second, the research team showed a link between the metabolism of fats and differences in DPSC aging. Both revelations are precursors to new tools that could be used to regulate aging in teeth, a key step toward a future of regenerative treatments for dental patients.
The clinical implications of the research were especially intriguing to Ammar Alghadeer, a PhD candidate in the Ruohola-Baker Lab. “As a dentist, it’s important to me to characterize these cells and determine how we can regulate them,” says Alghadeer, who will return to Saudi Arabia to research and practice dentistry after earning his doctorate. “That could lead to new ways of treating everything from cavities to helping people with more serious diseases that affect the teeth.”
Yan Ting (Blair) Zhao, another PhD candidate who contributed to the study, spoke further to the real-world implications of the team’s findings. “From a patient point of view, the more we understand about DPSCs, the more we can do to repair injured teeth, or even someday grow a whole new tooth. That’s future we’re hopeful for.”
Dr. Hai Zhang, an Associate Professor of Restorative Dentistry in the UW School of Dentistry, agrees the results of the study are a significant step forward in research that could have exciting implications. “Regulation is the key to regenerative dentistry,” says Dr. Zhang. “We have to understand how to control each aspect of these stem cells before we can safely utilize them in clinical treatments.”
Currently, Dr. Zhang and the Ruohola-Baker lab are building on the findings of the study. In an ongoing collaboration, they are exploring how to grow human stem cells into ameloblasts, cellular structures that produce enamel, the outer layer of the tooth that is vulnerable to decay.
Vanessa Chrepa, an Assistant Professor of Endodontics in the UW School of Dentistry, spoke to the importance of the study for her field. “The identification of slow and fast aging cells within the same age group of donors is a fascinating outcome. It means that factors other than patient age may contribute to the aging mechanisms. Modulation of theTGF pathway may lead to novel therapeutic approaches for dental pulp regeneration.”
Dr. Georgios A. Kotsakis, Associate Professor of Periodontics at UT Health San Antonio, also points to the clinical significance of understanding the role of the TGF pathway in DPSC aging. “Regenerative Endodontic procedures are currently limited to young persons with immature roots because of a lack of comprehensive understanding of DPSC aging and avenues for its modulation in older adults. The present findings reveal for the first time that TGF pathway modulation may be a viable strategy to prevent stem cell aging and increase metabolic activity, and potentially lead to successful regenerative treatments irrespective of patient’s age.”
While there are many problems to solve before regenerating full teeth becomes a reality, the new knowledge about the mechanisms of DPSCs may well revolutionize prospects for everyone from a young hockey player to a patient with a genetic disease that causes enamel deficiency.
This work is supported in part by the University of Washington’s Proteomics Resource (UWPR95794). RTM is an Investigator of the HHMI. This work is supported in part by grants from CoMotion Innovation Fund, the National Institutes of Health R01GM097372, R01GM97372-03S1 and R01GM083867, 1P01GM081619 and the NHLBI Progenitor Cell Biology Consortium (U01HL099997; UO1HL099993) for HRB.