June 16, 2008

Stem Cells May Help Rebuild Damaged Bone

CHAPEL HILL, N.C. -- When Harry Potter breaks his arm in a Quidditch match, the Hogwarts nurse gives him a magic potion called "Skelegro." In the morning, his arm is good as new.

The possibility of using a potion like Skelegro to treat severe bone fractures may soon be more than the stuff of wizard tales. Medical researchers at University of North Carolina-Chapel Hill announced Monday that they have made strides in the technology to rebuild damaged bone tissue using stem cells.

The research team, led by Dr. Anna Spagnoli, an associate professor of pediatrics at the university, derived the stem cells from bone marrow samples to locate and repair broken bones in mice. Now the work is poised to move to humans.

"What we have done here is shown a reason to move to a real clinical trial," Spagnoli said.

Twenty percent of broken bones cannot heal on their own, which affects 600,000 people in the United States each year. A significant portion of them are women who suffer from osteoporosis, but the problem is not restricted to older patients. Children diagnosed with a condition known as brittle bone disease can suffer from multiple, painful fractures over their lifetimes.

Stem cell technology could significantly reduce healing time, Spagnoli said, noting that the development could also help trauma patients.

It's a field that is generating interest, and possibilities. A recent case in Germany, in which a man lost his jaw to an aggressive tumor, was reported in the journal Lancet in 2004. In that instance, German scientists used a titanium jaw prosthesis as a scaffold in which they planted stem cells extracted from the patient's bone marrow. The scaffold served as a mold for a new jawbone to grow from the cells.

"These cases are very promising, but one case does not make science," Spagnoli said.

The University of North Carolina study coaxed the stem cells to become cartilage using a compound called a growth factor.

"The first step in bone healing is to create cartilage as a glue," Spagnoli said. "Without that glue, the bone will not be able to heal."

But just creating cartilage is not enough to fix a broken bone. The cartilage glue needs to form at the fracture for it to heal properly.

"Nobody knew if the stem cells would even go to the place where they were needed _ the fracture," Spagnoli said. To address this, Spagnoli's team injected a group of healthy mice with the same substance that makes fireflies glow. When they extracted bone marrow from these glow-in-the-dark mice, they got glow-in-the-dark stem cells, which the researchers then injected into ordinary mice with bone fractures.

"We put the mice in a dark box and we saw the light, and we could see it was going to the right place," Spagnoli said. "When we saw (this), we were so excited, we celebrated with a bottle of good Spanish wine."

But how do the stem cells know where to go when they are injected into the body? Spagnoli's team noticed that a certain molecule in the stem cells was the key to homing in on the fracture. The molecule, called CXR4, was responding to a chemical signal sent out by the damaged bone.

"It's like the fracture is sending out a message that says 'please come here, there is help needed here,'" Spagnoli said.

Elizabeth Loboa, an assistant professor of biomedical engineering at North Carolina State University who studies the effect of mechanical stress on stem-cell tissue generation, said she was intrigued by the University of North Carolina results.

"You always have the challenge of going from the animal to the human model, depending on the research," said Loboa, who was not involved in Spagnoli's research. "But this sounds very promising. There's a lot of exciting research going on in North Carolina on tissue engineering right now, especially in the Triangle area."

Spagnoli hopes that this technology will be approved by the Food and Drug Administration for clinical trial as soon as possible.

"We have another bottle of good Spanish wine all ready for when the study is published," she said.