A baby's not a baby anymore when its first temporary tooth drops out. If the child wisely slips that dental souvenir under the pillow that night, then the Tooth Fairy swaps it for a small sum of money.

By sheer serendipity, this is what happened years ago to the then-6-year-old daughter of pediatric dentist Songtao Shi, a researcher at the National Institutes of Health. "It happened one evening," he recalled, "when [daughter] Julia asked for my help in pulling out a loose baby tooth. Once it was free, we sat and looked carefully at her tooth," Shi recounted. " Wait a minute, Julia,' I said, there is some red-colored tissue inside your tooth.' So I took that exfoliated incisor to my laboratory the next day at the NIH Craniofacial and Skeletal Diseases Branch, and examined it. Sure enough, it had beautiful pulp tissue left over!

"A few days later," Shi continued, "when another of Julia's baby teeth came out, I was better prepared. I placed that tooth into a liquid culture medium and extracted the dental pulp. Soon thereafter, I succeeded in isolating living stem cells from the tissue. That discovery led to the isolation and collection of many more exfoliated teeth from Julia and other 7- to 8-year-old children. Although stem cells are abundant during embryonic development," Shi observed, "finding postnatal stem cells is a focus of current research."

Shi is senior author of an article in the latest Proceedings of the National Academy of Sciences (PNAS), released online April 22, 2003. Its title: "SHED: Stem cells from human exfoliated deciduous teeth."

"Our finding reports for the first time," Shi told BioWorld Today, "that the temporary teeth children begin losing around their sixth birthday contain a rich supply of stem cells in the dental pulp. This unexpected discovery," he added, "could have important implications, because the stem cells remain alive inside the tooth for a short time after it falls out of a child's mouth. This suggests those cells could be readily harvested for research."

SHED' Means Simply Stem Cells From Baby Teeth

Shi and his co-authors named the childhood cells SHED, which, he explained, stands for "stem cells from human exfoliated deciduous teeth." Deciduous is the formal term for the colloquial baby teeth.

"Children normally develop a set of 20 deciduous teeth," Shi noted, "which appear around six months after birth and generally are replaced, one tooth at a time, between ages 6 and 12.

"For years," Shi pointed out, "doctors have successfully harvested stem cells from umbilical cord blood. Our finding," he noted, "is similar in some ways, in that the stem cells in the tooth are likely latent remnants of an early developmental process.

"The stem cells are unique compared to many adult' stem cells in the body," Shi went on. "They are long-lived, grow rapidly in culture, and with careful prompting in the laboratory, have the potential to form specialized dentin and induce bone and neuronal cells. If follow-up studies extend these initial findings, we may have identified an important and easily accessible source of stem cells that possibly could be manipulated to repair damaged teeth structures, induce the regeneration of bone and treat neural injury or disease."

Shi and his co-authors launched an initial round of studies to determine whether the cells would grow well in culture. Using dental pulp extracted from children's deciduous incisors, they discovered that about 12 to 20 stem cells from each tooth reproducibly had the ability to colonize and grow in vitro. They also found that the SHED teeth behaved much differently than their earlier research. They grew much faster and doubled their populations in culture at a greater rate, suggesting SHED may be in a more immature state than adult stem cells.

"The unique SHED acronym," Shi made clear, "was needed to differentiate the deciduous stem cells from those in adult tissues, such as bone or brain. Stem cell research has exploded during the past seven or eight years," Shi said, "yet people still talk in general terms of postnatal' and adult' stem cells as though they are one and the same. Postnatal cells from children may act totally different than adult stem cells."

The team soon found that those cells could be prompted to express proteins on their surface, indicative of stem cells that were in the process of switching into bone and dental pulp cells. This discovery led to follow-up in vivo mouse experiments to determine whether SHED also possessed the potential to switch into neural and fat cells, and precursors to tooth cells. The cells responded accordingly.

The team injected human SHED and collateral chemicals into the brains of nude, immunocompromised mice. "Because they do not have immune rejection, we saved the human stem cells for future use on the same person," he said. "We do not know what those cells will do after 10 or 20 years. But we do know that these stem cells do have some function. For example, they can become immune cells. And from the dentin tooth ivory they can induce bone. The transplants," Shi recounted, "yielded human-specific odontoblasts for bone regeneration."

Teeth, Brain Share Same Precursor Partners

"It is notable," he added, "that SHED expressed neuronal and glial markers, which may be related to the neural-crest-cell origin of the dental pulp. Those brain cells," he pointed out, "play a pivotal role in embryonic development, giving rise to a variety of cell types such as neural cells, pigment cells, smooth muscle, craniofacial cartilage and bone. Dental pulp cells," Shi noted, "are known to produce neurotrophic factors, and even rescue motoneurons after spinal cord injury.

"These data are just the start," he affirmed. "We're trying now to characterize more fully which cell types can be generated from these stem cells. Can they be switched into nerve and glial cells only? We need to find this out. In current ongoing work, we are just looking for more dental stem cell functions for therapy - what they can do; what they can't.

"Here at NIH," Shi pointed out, "we are working for the government. We are looking for some company interested in doing this work." His discoveries are patent pending. "As a scientist and a clinician," he concluded, "I would really like to say that what we have found can be transferred to clinical application."