Adult Stem Cells Aid Broken Bone

Adult Stem Cells Aid Broken Bone

TUESDAY, 17 JUNE 2008
UNC study lays groundwork for potential treatments
Tuesday, 17 June 2008

In an approach that could become a new treatment for the 10 to 20 percent of
people whose broken bones fail to heal, researchers at the University of
North Carolina at Chapel Hill have shown that transplantation of adult stem
cells can improve healing of fractures.

Adult stem cells are specialized cells with the ability to regenerate tissue in
response to damage. However, many patients lack sufficient numbers of
these cells and thus cannot heal properly.

Researchers have used adult stem cells in a few cases to improve fracture
healing, but further studies were needed to show that this method was truly
effective and safe before it can be pursued as a new treatment. Now
scientists at UNC have provided the scientific foundation for future clinical
trials of this approach by demonstrating in animal models that these cells can
be used to repair broken bones.

"This finding is critical to patients who lack the proper healing process and
to individuals prone to broken bones, such as those with osteoporosis and
the rare genetic condition known as brittle bone disease," said Dr. Anna
Spagnoli, associate professor of paediatrics and biomedical engineering in
the UNC School of Medicine and senior author on the study.

The study, presented Monday, June 16 at the annual Endocrine Society
meeting in San Francisco by the first author, Froilan Granero-Molto, Ph.D.,
post-doctoral associate researcher in UNC's paediatrics department, is the
first to visualize the action of transplanted adult stem cells as they mend
fractures in mice.

During normal fracture healing, stem cells migrate to the site of the break,
forming the cartilage and bone needed to fuse the broken bones back
together. But in more than 600,000 Americans a year, this process does not
occur as it should and these bones stay broken. The result can be long
periods of immobilization, pain, bone deformities and even death.

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Current therapies, such as multiple surgeries with bone autografts and
artificial prosthetic materials, often are not enough to cure these patients.

"Man-made materials do not address the normal bone's function, and
recurrent fractures, wear and toxicity are a real problem," Spagnoli said.

"There is clearly a need to develop alternative therapies to enhance fracture
healing in patients with bone union failure."

Kicking stem cells into repair mode is one of the objectives of a new branch
of medicine called regenerative medicine. With a little prodding, stem cells
in human bone marrow – called mesenchymal stem cells – can turn into
bone, cartilage, fat, muscle and blood vessel cells.

"The beauty of regenerative medicine is that we are helping the body
improve its innate ability to regenerate healthy tissue on its own, rather than
introducing manmade materials to try to patch up a broken bone," Spagnoli
said.

Granero-Molto and other colleagues led by Spagnoli demonstrated this
approach by transplanting adult stem cells in mice with fractures of the tibia,
the long bone of the leg. The cells were taken from the bone marrow of mice
that produce luciferase, the same molecule that allows fireflies to glow. In
addition to possessing the ability to glow, the cells were engineered to
express a molecule called insulin-like growth factor 1 (IGF-1). IGF-1 is a
potent bone regenerator necessary for bones to grow both in size and
strength.

The researchers transplanted the cells through a simple intravenous injection
and then placed the mice into a dark box so they could track the glowing
stem cells as they migrated within the rodent. They found that these cells
were specifically attracted to the fracture site, and that a particular molecule
called CXCR4 – which acts as a homing signal – was necessary for the
migration.

Using a computerized tomography (CT or CAT) scan, the researchers
showed that the stem cells not only migrated to the site of the fracture, but
also improved healing there by increasing the bone and cartilage that bridged
the bone gap. The bone at the fracture site in the treated mice was about

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three times stronger than that of untreated controls.

If scientists can duplicate the results of this animal study in humans, it may
lead to a new treatment for the millions of people who suffer fractures that
do not heal properly, Spagnoli said. Once a physician determines that the
bone has not healed, they could obtain adult stem cells from the person's
bone marrow in a minimally invasive procedure and transplant them at the
same time the patient is receiving a bone graft.

Spagnoli said adult stem cells may pose fewer problems than embryonic
stem cells, since they are not associated with the ethical controversy that
surrounds the latter. Also, they may avoid the problem of rejection by the
immune system, since the patient's own cells can be used.

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