Photo of a tooth
germ with a nylon noose (left) and the noose tightened (right)
(December 18, 2015) Researchers
from the RIKEN Center for Developmental Biology, working with colleagues from
the Tokyo Medical and Dental University, have found a way to—literally—multiply
teeth. In mice, they were able to extract teeth germs—groups of cells formed
early in life that later develop into teeth, split them into two, and then
implant the teeth into the mice’s jaws, where they developed into two fully
functional teeth.
Teeth are a major target of regenerative medicine. According
to Takashi Tsuji, the leader of the team, approximately 10 percent of people
are born with some missing teeth, and in addition, virtually all people lose
some teeth to either accidents or disease as they age. Remedies such as
implants and bridges are available, but they do not restore the full functionality
of the teeth. Growing new teeth would be beneficial, but unfortunately humans
only develop a limited number of teeth germs—the rudimentary cell groups from
which teeth grow.
CT cross-sections
of a natural tooth (right) and split tooth (left)
“We wondered,” says Tsuji, “about whether we might be able
to make more teeth from a single germ.” To demonstrate that it might be
feasible, the group focused on the fact that teeth development takes place
through a wavelike pattern of gene expression involving Lef1, an activator, and
Ectodin, an inhibitor. To manipulate the process, they removed teeth germs from
mice and grew them in culture. At an appropriate point in the development
process, which turned out from their experiments to be 14.5 days, they nearly
sliced the germs into two with nylon thread, leaving just a small portion
attached, and continued to culture them. The hope was that signaling
centers—which control the wave of molecules that regulate the development of
the tooth—would arise in each part, and indeed this turned out to be true. The
ligated germs developed naturally into two teeth, which the team transplanted
into holes drilled into the jaws of the mice. The teeth ended up being fully
functional, allowing the mice to chew and feel stimulus, though they were only
half the size of normal teeth, with half the number of crowns—a result that
could be expected given that the researchers were using already developed
germs.
Significantly, they were able to manipulate the teeth using
orthodontic methods, equivalent to braces, and the bone properly remodeled to
accommodate the movement of the teeth.
3D (top) and
cross-sectional (bottom) CT images of the transplants growing in the jaw
Looking to the future, Tsuji says, “Our method could be used
for pediatric patients who have not properly developed teeth as a result of
conditions such as cleft lip or Down syndrome, since the germs of permanent
teeth or wisdom teeth could be split and implanted. In the future, we could
also consider using stem cells to grow more germs, but today there are barriers
to culturing such cells, which will need to be overcome.”