Adult stem cells aid fracture healing; UNC study lays groundwork for
potential treatments
CHAPEL HILL – 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 pediatrics
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 pediatrics
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.
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 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.
###
Funding for the study came from the National Institutes of Health.
Other co-authors of the study include Dr. Lara Longobardi, UNC
assistant professor of pediatrics, along with the following
researchers from Vanderbilt University: Dr. Michael Miga, assistant
professor of biomedical engineering; Dr. Jared A. Weis, postgraduate
fellow in biomedical engineering; Benjamin Landis, medical student;
and Lynda O'Rear, research specialist.
School of Medicine contacts: Stephanie Crayton, (919) 966-2860,
scrayton@unch.
News Services contact: Patric Lane, (919) 962-8596,
patric_lane@
Public release date: 16-Jun-2008
Contact: Stephanie Crayton
scrayton@unch.
919-966-2860
University of North Carolina at Chapel Hill
http://www.eurekale
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StemCells subscribers may also be interested in these sites:
Children's Neurobiological Solutions
http://www.CNSfoundation.org/
Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123
The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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