Medical science may be about to achieve two things once thought impossible.
One is re-growing teeth, something that would eliminate the need for dental fillings.
The other is healing surgical wounds without leaving scars, a process that involves using a drug designed to treat Alzheimer’s disease.
Teams of scientists in England and the United States, following years of research with mice, announced these discoveries this month.
They hope to begin clinical trials soon.
No more scars?
Researchers at the University of Pennsylvania’s Perelman School of Medicine say they have discovered a way to manipulate wounds to heal as regenerated, normal skin rather than as unsightly scar tissue.
The scientists transformed the most common type of cells found in wounds into fat cells. This had been considered impossible to accomplish in humans.
The research team conducted a large, multiyear study in collaboration with the Plikus Laboratory for Developmental and Regenerative Biology at the University of California, Irvine.
They published their findings in early January in the journal Science.
“We can manipulate wound healing so that it leads to the regeneration of normal skin without scars,” said Dr. George Cotsarelis, who chairs the Department of Dermatology at Penn, and is the Milton Bixler Hartzell Professor of Dermatology, and principal investigator of the project.
“The secret is to regenerate hair follicles first,” he told Healthline. “Then the fat will regenerate in response to the signals from those follicles.”
Fat cells called adipocytes are normally found in the skin, Cotsarelis said, but they are lost when wounds heal as scars. Myofibroblasts, the most common cells found in healing wounds, were thought to form only scars.
“Scar tissue does not have hair follicles associated with it, which gives it an abnormal appearance from the rest of the skin,” he said.
Cotsarelis and his colleagues used these characteristics as the basis for their work. Their goal was to change the already present myofibroblasts into fat cells, which do not cause scarring.
“Our study showed hair and fat develop separately but not independently,” he said. “Hair follicles form first, and we previously discovered factors necessary for their formation.”
While Cotsarelis and his colleagues tried to determine what was sending the signal from the hair to the fat cells, they identified a factor called bone morphogenetic protein, which instructs the myofibroblasts to become fat.
This signaling was groundbreaking on its own, he said, as it changed what was previously known about myofibroblasts.
Now his team has discovered additional factors produced by the regenerating hair follicles that convert the surrounding myofibroblasts to regenerate as fat instead of forming a scar, he said.
“That fat will not form without the new hairs,” he said. “But once it does, the new cells are indistinguishable from the preexisting fat cells, giving the healed wound a natural look instead of leaving a scar.”
The potential for applying his research goes beyond preventing scars.
Cotsarelis said their discoveries also could make it possible to regenerate adipocytes in wrinkled skin, especially in the face, leading to new anti-aging treatments.
Cotsarelis is also co-founder of Follica, Inc., a Boston-based company that is developing a system to treat hair loss and to stimulate the growth of new hair follicles.
He has filed for a patent and said clinical trials may be eventually conducted at Penn.
“We looked at isolated molecules from keloids, which are very big benign tumors that form on pierced ears, and are sometimes the size of golf balls,” Cotsarelis said. “If we can convert those cells to fat, it will be easier to treat scarring, including cancer surgery scars."
No more dental fillings?
In England, scientists at King’s College London have discovered a new method to stimulate the renewal of living stem cells in tooth pulp by using an Alzheimer’s drug.
In a paper published this month in Scientific Reports, the researchers detailed their method to stimulate the stem cells inside tooth pulp to generate new dentine — the mineralized material that protects the tooth — in large cavities.
This could potentially reduce the need for fillings or cements.
Professor Paul Sharpe, Ph.D., lead author of the ongoing three-year study, specializes in molecular control of tooth development, tissue engineering, and dental stem cells in the college’s Department of Craniofacial Development and Stem Cell Biology.
“When a tooth suffers trauma or infection, the soft, inner pulp can become exposed and infected,” Sharpe told Healthline. “The body reacts to protect the tooth and produces a thin band of dentine that seals the tooth pulp. This natural process, however, is insufficient to repair large cavities effectively.”
Dentists use man-made cements or fillings to treat larger cavities and fill holes in teeth, he said. But the cement remains in the tooth and does not disintegrate, so the tooth’s normal mineral level is never completely restored.
Sharpe and his colleagues found that teeth could use their natural ability to repair large cavities without cements or fillings, which are prone to infections and often need to be replaced a number of times.
“When fillings fail or infection occurs, dentists have to remove and fill an area that is larger than what is affected, and after multiple treatments the tooth may eventually need to be extracted,” Sharpe said. “As this new method encourages natural tooth repair, it could eliminate all of these issues, and provide a more natural solution for patients.”
How did an Alzheimer’s drug, tideglusib, become a candidate for dentine regeneration?
One of the small molecules the team used to stimulate the renewal of the stem cells included tideglusib, which has been used in clinical trials to treat neurological disorders such as Alzheimer’s disease.
This presents an opportunity to fast track the treatment into practice, Sharpe said.
The scientists used biodegradable collagen sponges to apply low doses of small-molecule glycogen synthase kinase inhibitors to the tooth.
“We found that the sponge degraded over time and that new dentine replaced it, leading to complete, natural repair,” Sharpe said.
Collagen sponges are commercially available and clinically approved. These factors, he said, add to the potential for this treatment to be adopted quickly and used in dental clinics.
Sharpe plans to seek funding for a clinical trial from the United Kingdom’s Medical Research Council, and will seek commercial partners to move the project forward.
Sharpe is optimistic about his discovery.
“The simplicity of our approach makes it ideal as a clinical dental product for the natural treatment of large cavities, by providing both pulp protection and restoring dentine,” he said. “It brings stem cell biology into clinical dentistry for the very first time, and will hopefully make the clinical dental community aware that biological-based treatments are the future.”