No wonder some orthopedists consider cartilage regeneration the holy grail
of their field. Confronted with hordes of
gimpy people living longer lives, orthopedists have used surgery to clean out
damaged joints, braces to
stabilize a wobbly gait and
artificial knees and hips
to replace damaged bone
ends, a last resort against
osteoarthritis. Everything
short of new cartilage.
But now, with the help
of stem cells, a new generation of bioengineers
are coming close to cracking the code for cartilage
regrowth. Stem cells have
yet to choose a career
path, a characteristic that
makes them attractive future cartilage-creators. The blue sky version of the
stem cell approach goes like this: Stem
cells are extracted from a patient, geared
up to become chondrocytes, wrapped in
a favorable mix of compounds and then
inserted into damaged joints. The cells
take it from there. Voilà: neo-cartilage.
Scientists have recently pinpointed
prominent proteins needed to keep stem
cells on track to becoming cartilage-making chondrocytes and have even
devised nanosized polymer scaffolds on
which these stem cells can start growing cartilage. The cells seem to behave
better if surrounded by molecules found
naturally in healthy cartilage, and some
research suggests scaffolding derived
from cartilage itself might deliver much-needed biochemical prompts.
SCOTT CAMAZINE/PHOTO RESEARCHERS, INC.
While still in the experimental phase,
the stem cell strategy is gaining ground:
More than a dozen clinical trials using
stem cells as cartilage regenerators are
under way or planned in Norway, Spain,
Iran, Malaysia, France and elsewhere.
Tissue engineering and cartilage
regeneration were at “point zero” in
the 1970s, says Wan-Ju Li, a tissue engineer at the University of Wisconsin–
Madison. “Now the technology is more
mature. All together, the field is getting
very rich and very interesting.”
Researchers aren’t interested in making just any cartilage. They want the
kind that caps the ends of long bones,
such as those in the legs. This type,
called hyaline cartilage, is distinct from
the bendable kind in the
ears or the fibrocartilage
found between vertebrae.
Hyaline cartilage is slippery, glassy, elastic and
smooth. Picture the tough
gristle at the rounded end of
a ham bone. It is everything
humans would want to cap
a bone in a weight-bearing
joint, allowing them to
move about like pain-free
machines.
But past attempts to
repair hyaline cartilage
through regeneration have come up
short. For decades, the surgical approach
for a damaged joint has been to clean
out frayed cartilage and, sometimes,
drill tiny holes into the worn ends of the
bone. The holes allow blood and stem
cells from bone marrow to leak out and
patch the injury.
In theory that should work, but the
stem cells seeping through the holes
lack focus. “Those stem cells that come
out are confused,” says John Sandy, a
biochemist at Rush University Medical
Center in Chicago. “They’re not getting
the right signals.… So they hit the middle
road.” They make fibrocartilage, a poor
substitute for hyaline. In a recent study,
only two-thirds of athletes receiving
this “microfracture surgery” following
injury showed good results, and only half
maintained their original level of play for
several years.
Doctors have also transplanted living
chondrocytes onto worn-out bone ends.
Genzyme, a biotech company based in
Cambridge, Mass., offers an off-the-shelf
kit for this procedure. It requires taking
thousands of live chondrocytes from
healthy cartilage elsewhere in the body,
culturing the cells in a dish to expand
their numbers and packaging them with
other products for insertion into the
trouble spot. Called autologous chon-
27
million
Number of
American adults
affected by
osteoarthritis
50
percent
Chance of getting
osteoarthritis
during your lifetime
drocyte implantation, the procedure has
outperformed microfracture surgery in
some studies, but some patients need
follow-up surgery and a nine-year study
of implantation patients found that 30
percent didn’t improve. The trouble
may arise because mature chondrocytes
lose their ability to produce cartilage if
expanded through too many generations, Li says.
Stem cells have an advantage there.
Like newly hired employees, they should
have plenty of productive years in store.
Key for scientists is finding a reliable way
to teach these blank slate cells to become
hyaline-producing chondrocytes.
Cellular prompting
Scientists can round up starter stem cells
from all over the adult body. Those found
in connective tissues such as cartilage,
tendons and the synovial membrane that
forms a sac enveloping joints have the
potential to make good chondrocytes.
But so might some less-obvious choices,
such as stem cells from bone marrow, fat
tissue and discarded umbilical cords.
Before sending them into the fray,
When cartilage wears away, bone
rubs on bone (as shown in this color-enhanced X-ray of a 76-year-old man’s
knee). Such rubbing is a sure sign of
budding osteoarthritis.
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August 11, 2012 | SCIENCE NEWS | 23
