The work has been conducted just in mice so far, but the research, published Monday in the journal Scientific Reports, highlights a way to motivate stem cells to repair tooth defects at a scale they normally can’t, with a drug that already has some safety testing behind it.
It also demonstrates the potential of a type of stem cell therapy in which the cells are stimulated in place, rather than taken out, manipulated, and put back in.
“We’re mobilizing stem cells in the body and it works,” said Paul Sharpe, a researcher at King’s College London and an author of the new paper. “If it works for teeth, chances are it could work for other organs.”
Experts not involved with the work noted that while it is in early stages, the simplicity of the approach should ease its path into the next phases of research that show whether it might produce the same results in people.
“These important steps close down the translational gap and bring this discovery a step closer to future clinical applications,” Dr. Vanessa Chrepa, a researcher at the University of Washington, wrote in an email. “This work will hopefully set the stage for clinical studies in the near future.”
When teeth lose some of their dentin — the bony tissue beneath the enamel that makes up the bulk of the tooth — the stem cells tucked deep inside mount a recovery effort and manufacture new dentin (which is also spelled dentine). The problem, Sharpe said, is that the natural repair mechanism can only regrow small amounts of dentin and can’t make up all that is lost when a tooth suffers a serious injury, contracts a major infection, or takes on the sharp end of a dentist’s drill.
“We’re mobilizing stem cells in the body and it works.”
Because of the limits of the teeth’s ability to repair themselves, dentists have to fill or seal teeth to prevent further infection and degradation. But dental cement also prevents the tooth from ever returning to its natural, pearly white self.
Sharpe and his team have been trying to understand how the natural repair mechanism works in hopes of converting that understanding into a way to super-power it. As part of their research, they discovered that a group of molecules called glycogen synthase kinase inhibitors (or GSK-3 inhibitors) boosts the stem cells’ ability to stimulate production of dentin beyond what normally occurs.
For the new study, the researchers drilled tiny holes into mice’s molars to expose the tooth’s pulp, where the stem cells live. They then inserted collagen sponges that had been soaked in one of three types of GSK-3 inhibitors and covered the tooth.
After six weeks, the researchers removed the teeth and found that the sponges had dissolved and the lost dentin had mostly been regenerated.
“They’ve harnessed the signaling pathway that promotes natural repair,” said Megan Pugach, a researcher at the Forsyth Institute in Cambridge, Mass., and at the Harvard School of Dental Medicine, who was not involved with the research.
Sharpe and his team are now conducting similar studies in rats to make sure the approach can generate enough dentin to fill in larger holes in larger teeth before trying to study the method in people. But two aspects of the approach could help ease its path into clinical trials.
First, the researchers used collagen sponges that are already commercially available and are shown to be safe. Secondly, one of the GSK-3 inhibitors they used, called Tideglusib, has been tested in people as a possible therapy for Alzheimer’s disease, meaning it is already shown to be safe in higher doses than what the researchers would incorporate into the sponge.
“In terms of getting that into the clinic, we can make a huge leap,” Sharpe said.
Sharpe and other researchers around the world have been studying if and how teeth stem cells could be used to regenerate a whole tooth, possibly one day replacing dentures or implants. But teeth are complex organs, with both hard and soft tissue, so that goal remains further away.
Because this approach is just focused on dentin, “it’s a bit more low-hanging fruit,” Sharpe said. But this study also adds to the possibility of stem cell therapies, which are much hyped, but for the most part have yet to be developed into validated treatments.
“This is a very clear, simple demonstration that with basic knowledge of what happens normally in the body, you can design something that can enhance that,” he said.