Baby Teeth Stem Cells Reverse Motor Deficits in Cerebral Palsy Model

The damage happens fast. Oxygen stops reaching the newborn brain, blood flow collapses, and within minutes the injury is done. What follows can take years to become fully visible: a child who struggles to walk, whose limbs resist the movements other children make without thinking, whose learning looks different from the inside. Cerebral palsy, the most common motor disability in childhood, affects roughly two to three babies in every thousand born, and there is currently no treatment that reverses it once symptoms appear.

That last clause may now need a caveat. Researchers at Nagoya University Hospital have shown, in rat models of the condition, that stem cells extracted from naturally shed baby teeth can improve motor function and learning even after the animals have already developed significant deficits. “This is the first animal study to show that stem cell treatment works even after motor deficits have already appeared,” says Clinical Professor Yoshiaki Sato, the study’s corresponding author.

The stem cells in question come from an unusual source. Dental pulp, the soft tissue at the core of a tooth, contains a population of mesenchymal cells that retain surprising developmental flexibility. In baby teeth that fall out naturally, those cells are otherwise lost. Clinical Professor Sato’s team, working with the Japanese biotech company S-Quatre, has been developing a therapy that harvests what would otherwise be thrown away. “These stem cells are collected from baby teeth that have naturally fallen out and would otherwise be discarded,” Sato says. “This method avoids the ethical concerns associated with other stem cell sources.”

The rat model used in this study was designed to replicate hemiplegic cerebral palsy. Seven-day-old pups had one carotid artery tied off, then spent an hour in low-oxygen conditions, producing one-sided brain injury and one-sided motor impairment. At four weeks, the team ran a horizontal ladder test, selecting only animals with scores significantly worse than healthy controls. Those rats were the ones that received treatment.

The stem cells, one million per dose, were injected intravenously three times over four weeks, at ages roughly corresponding to pre-adolescence in human terms. No immunosuppressive drugs were used. The team then waited.

By four months, the treated animals were crossing the ladder with fewer slips than untreated controls. The cylinder test, which measures how much a rat favors its unimpaired limb, showed the treated group relying more on the side that had been affected. Perhaps most striking: in the shuttle avoidance task, where rats learn to escape an electric shock by moving to the other side of a box, the SHED group outperformed controls in later sessions, suggesting recovered learning capacity rather than just improved movement.

The question was how. Tracking cells labeled with quantum dots, the team confirmed that intravenously administered stem cells cross into the brain, peaking there twenty-four to forty-eight hours after injection. Proteomic analysis of brain tissue two weeks after treatment found sixty-one proteins changed significantly in treated animals compared to controls; the most strongly enriched cluster of changes was tied to neurogenesis, the birth of new neurons. Histology confirmed it: more immature neurons were forming in the hippocampus and striatum of treated rats shortly after the injections, and more mature neurons were present ten weeks later. Staining for an apoptosis marker showed no difference between groups, so the extra neurons weren’t explained by less dying. They were explained by more being born.

The mechanism runs through a growth factor called HGF. SHED secrete it at much higher levels than bone marrow stem cells or dermal fibroblasts, and when the team blocked HGF, either with a neutralizing antibody or by knocking out the gene that produces it, the stem cells’ ability to promote neural stem cell growth collapsed. Replacing HGF restored it. The pathway downstream runs through a signaling cascade, PI3K-Akt, that normally keeps new cells cycling and growing.

What makes this notable, beyond the reversal of symptoms, is the timing. Previous stem cell research has focused on the acute and subacute phases of brain injury, the weeks immediately after birth. Clinical protocols for those windows exist but leave behind a much larger population: children diagnosed months or years later, after the initial injury has long since settled into chronic damage.

Nagoya University Hospital is now running a Phase 1 safety trial in children with cerebral palsy, giving a single intravenous dose of autologous SHED, meaning cells taken from the child’s own baby teeth. The next steps, pending safety data, would be larger trials. “Our ultimate goal is to establish this approach as a new treatment option for patients with cerebral palsy and their families,” Sato says.

There are distances still to close. Rat brains and human brains differ in ways that matter for neurogenesis, and the pro-growth properties of HGF carry their own safety questions about tumor risk that future trials will need to track carefully. The window for collecting baby teeth is narrow, and supply will eventually require standardization. But somewhere in those small, discarded teeth is a signal the brain can still hear.

Study link: https://doi.org/10.1186/s13287-025-04828-y