Science News - August 11, 2012

M
S
X
S

For the pigs By implanting biodegradable polymer scaffolding seeded with stem cells, researchers were able to regrow lost cartilage in the knee of a pig. Six months after the damage (arrows), the joint treated with the scaffold and stem cell combination (X) showed better cartilage regrowth than did a joint treated with scaffolding seeded with mature chondrocytes (M) or joints with scaffolding alone (S).

became interested in building a synthetic scaffold resembling the naturally occurring one, onto which they could seed stem cells. While still at the National Institutes of Health, they used a process called electrospinning to cast nanofibers of polymer into a structure resembling cartilaginous matrix. Those first webs have since been improved and made into a biodegradable cartilage scaffold.

“It’s easy to fabricate and there’s no batch-to-batch difference,” Pei says.

Li notes that the polymer, built to degrade after six to 12 months in the body, has strong mechanical properties that keep stem cells together, giving the cells time to weave their own matrix of cartilage.

In 2009, Tuan and Li tested their scaffold, seeding it with human stem cells to create a patch that was then inserted into pigs with cartilage damage in their knees. Some pigs received scaffolding seeded with mature chondrocytes. The researchers allowed the pigs, with some restrictions, to put weight on the knees almost immediately, since routine compression is the norm for cartilage.

After six months, the stem cells had grown into chondrocytes that made hyaline cartilage that outperformed the fibrocartilage made by the mature chondrocytes.

“It was glassy cartilage,” Li says, “with
good mechanical properties.”
In an alternative approach, other
researchers are testing the scaffold
potential of a cartilage matrix obtained
from cadavers. The scientists remove the
cells and use the rest. Though that work
is in its early stages, Pei says the natural
matrix offers some useful biological cues
for stem cells that a polymer doesn’t.

Early adapters

Once that goal is achieved, one of the big challenges will be to determine which patients would benefit most from the treatment. Much osteoarthritis seems to unfold over a lifetime, but many patients develop it from hyaline cartilage damage traceable to an injury. If cartilage regeneration reaches the clinic, treating these patients early could prevent further loss of cartilage and prevent osteoarthritis from overtaking the joint, says David Felson, a rheumatologist at Boston University School of Medicine.

Cartilage is made to handle stress
and compression, but every tissue has
its limits, and knee injury increases by
sixfold the likelihood that a person will
develop osteoarthritis. Felson says his
team has found evidence that injuries to
the knee structures “probably account
for a great majority of osteoarthritis.”
But early detection isn’t easy since
many people ignore or underestimate
their injuries. Years can pass before
X-rays and other scans show two bones
rubbing together, a sign of painful carti-
lage loss and budding osteoarthritis.

Carla Scanzello, a rheumatologist at Rush University Medical Center, and colleagues reported last year that inflammatory molecules that gradually destroy cartilage flood an injured joint and leave a telltale signature long before symptoms of osteoarthritis arise. Understanding these markers of inflammation “might help us target patients,” she says.

For the moment, that targeting would involve anti-inflammatory drugs to limit the cartilage degradation. But in the future, a stem cell treatment might dramatically reduce the number of people who end up needing a joint replacement, says Dobrila Nesic, a molecular biologist at the University of Bern in Switzerland.

An artificial knee or hip can last 10 to
15 years, Nesic says, and a person can get
two (per joint) in a lifetime. “If you’re
60, no problem,” she says. “If you’re 40,
your lifetime before wheelchair is 20 to
30 years.”
Researchers agree more work is
needed to bring stem cell–based carti-
lage regeneration to the clinic. Li sus-
pects the technical problems might be
solved in the next five years or so, with
another five years needed to sort out
regulatory and insurance issues.

He has students who are surgeons, still busy learning how to replace knees and hips. “I was joking with them,” Li says, “saying, ‘ You guys are going to have to find a new job soon.’ ” s