Spring 2013 - Tufts University School of Dental Medicine

leading-edge science
regeneration
multipurpose cells could act as biological repair
kits, treating diseases that won’t get better on
their own by David Levin
for most of us, minor
wounds are just an inconvenience.
We endure the minor
pain of a cut or scrape, stick on
a bandage and within a week,
our skin looks like nothing ever
happened.
In some cases, though,
healing isn’t so simple.
Somewhere along the way,
the complex chain of events
that lets the body repair itself
breaks down, and a wound
remains open, raw. Such is
the case with those who suffer
from chronic foot ulcers, a
nonhealing wound common
in diabetics.
“For these foot ulcers,
there are a variety of therapies,
but they are only successful
in roughly half the cases,
and [the ulcers] have a high
recurrence rate,” says Jonathan
Garlick, head of the Division
of Cancer Biology and Tissue
Engineering at Tufts School of
Dental Medicine. If the wound
doesn’t heal, sometimes the
only recourse is to amputate
the limb.
Garlick’s research could one
day help patients avoid that
kind of traumatic outcome.
He studies pluripotent stem
cells—a type of all-purpose
A microscopic view
of fibroblast cells
grown from a patient’s
nonhealing, diabetic
foot ulcer.
cell that has the potential to
become any type of tissue in the
human body. Once cells like
these are harnessed in the lab,
he says, researchers can implant
them directly into damaged
tissue to stimulate healing.
It’s a radical new way
of thinking about treating
disease, and it offers possible
cures for chronic conditions
that may not otherwise heal
on their own‚ from diabetic
foot ulcers to heart disease
and even periodontal disease,
where lingering inflammation
can lead to bone and gum loss.
“There are millions of
patients suffering from chronic,
nonhealing conditions like
these,” says Garlick, a professor
of oral and maxillofacial
pathology. “That suggests that
we have a lot of work to do.”
The challenges he and other
pluripotent stem cell researchers
face, however, have often
been more political than scientific.
Until several years ago,
the only way to obtain such
cells has been to harvest them
from human embryos that are
several days old; those tiny
balls of cells ultimately grow
into muscle, nerves, skin and
bone in the womb. Because
embryos develop from fertilized
human eggs, opponents
of their use in research argue
that scientists should not be
allowed to work with them
in the lab, a stance that has
sparked heated debate over the
embryo’s role in the quest for
stem cell therapies.
Garlick’s research, however,
might allow scientists to sidestep
these moral conundrums.
Using a process Japanese
researchers developed in 2006,
he and his team “reboot” cells
from freshly removed foreskins
(yes, foreskins), forcing
them to revert to an embryonic
cell-like state by adding four
genes to the cells’ DNA. The
resulting cells, called induced
pluripotent stem (iPS), acquire
the ability to develop again
into different kinds of cells.
“These alternative cells are
really at the crux of our scientific
questions,” says Garlick.
“Are induced pluripotent
stem cells the equivalent to
embryonic stem cells in terms
of their potential therapeutic
value Do they hold the same
promise for human therapies
in the future”
To find out, Garlick and
his colleagues are trying to
better understand some of the
biochemical processes that let
the cells “reboot” in the first
place. He says it all goes back to
DNA—or rather, the myriad
ways that cells interpret DNA.
Genetic Recipes
As you may remember from
high school biology, the information
in a DNA molecule is
a master plan for the entire
body. It’s a genetic cookbook
of sorts—inside, it contains
recipes for creating bone cells,
muscle cells, skin cells or any
other type of cell. Somehow,
though, in the face of all this
raw information, cells know
exactly where to start reading.
A healthy liver cell homes
8 tufts dental medicine spring 2013