Alligators may help scientists
learn how to stimulate tooth regeneration in people, according to new research
led by the Keck School of Medicine of USC.
For the first time, a global team of researchers led by USC pathology
Professor Cheng-Ming Chuong, M.D., Ph.D., has uncovered unique cellular and
molecular mechanisms behind tooth renewal in American alligators. Their study,
titled "Specialized stem cell niche enables repetitive renewal of
alligator teeth," appears in
Proceedings of the National Academy
of Sciences, the official journal of the United States National Academy of
Sciences.
"Humans naturally only have two sets of teeth -- baby teeth and adult
teeth," said Chuong. "Ultimately, we want to identify stem cells that
can be used as a resource to stimulate tooth renewal in adult humans who have
lost teeth. But, to do that, we must first understand how they renew in other
animals and why they stop in people."
Whereas most vertebrates can replace teeth throughout their lives, human
teeth are naturally replaced only once, despite the lingering presence of a
band of epithelial tissue called the dental lamina, which is crucial to tooth
development. Because alligators have well-organized teeth with similar form and
structure as mammalian teeth and are capable of lifelong tooth renewal, the
authors reasoned that they might serve as models for mammalian tooth
replacement.
"Alligator teeth are implanted in sockets of the dental bone, like human
teeth," said Ping Wu, Ph.D., assistant professor of pathology at the Keck
School of Medicine and first author of the study. "They have 80 teeth,
each of which can be replaced up to 50 times over their lifetime, making them
the ideal model for comparison to human teeth."
Using microscopic imaging techniques, the researchers found that each
alligator tooth is a complex unit of three components -- a functional tooth, a
replacement tooth, and the dental lamina -- in different developmental stages.
The tooth units are structured to enable a smooth transition from dislodgement
of the functional, mature tooth to replacement with the new tooth. Identifying
three developmental phases for each tooth unit, the researchers conclude that
the alligator dental laminae contain what appear to be stem cells from which
new replacement teeth develop.
"Stem cells divide more slowly than other cells," said co-author
Randall B. Widelitz, Ph.D., associate professor of pathology at the Keck School
of Medicine. "The cells in the alligator's dental lamina behaved like we
would expect stem cells to behave. In the future, we hope to isolate those
cells from the dental lamina to see whether we can use them to regenerate teeth
in the lab."
The researchers also intend to learn what molecular networks are involved in
repetitive renewal and hope to apply the principles to regenerative medicine in
the future.
The authors also report novel cellular mechanisms by which the tooth unit
develops in the embryo and molecular signaling that speeds growth of
replacement teeth when functional teeth are lost prematurely. Co-authors
include colleagues from the Louisiana Department of Wildlife and Fisheries,
University of
Georgia,
National Cheng
Kung University,
National Taiwan
University, and
Xiangya
Hospital in
China.
Reference:
The research was supported by the National Institute of Arthritis and
Musculoskeletal and Skin Diseases through grants 5R01AR042177-19,
5R01AR060306-03 and 2R01AR047364-11A1.
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