Firefly’s glow reveals stem cell role in mending fractures

Leigh MacMillan, Ph.D.
Published: February, 2006

A bone fracture appears to be a relatively simple medical problem to solve: cast it, wait, and everything will be fine. For about 10 percent of fracture patients though, healing doesn’t come easily. These patients, 600,000 people every year in the United States, require bone grafts or synthetic prostheses to mend their breaks.

Anna Spagnoli, M.D., assistant professor of Pediatrics and Cancer Biology, has another idea. She wants to use stem cells, harvested from a patient’s bone marrow, to aid fracture healing.

“As a pediatrician, I am especially interested in using stem cells to treat children with severe bone diseases like osteogenesis imperfecta,” a genetic disorder characterized by bones that break easily, Spagnoli says.

Investigators have known for 30 years that bone marrow contains two types of stem cells—the better known variety that repopulates the blood and another sort called mesenchymal stem cells that can become bones, cartilage, muscle, and even neurons, she explains. The potential of these cells to form cartilage is of particular importance for fracture healing, since cartilage grows as a “template” for new bone growth.

Spagnoli and colleagues turned to bioluminescence imaging to track mesenchymal stem cells in a mouse fracture model. They watched as the cells migrated through the animal and homed to the injured site after three days.

“This was an extremely important observation because homing of mesenchymal stem cells had never before been clearly demonstrated,” Spagnoli says. Bioluminescence imaging has also allowed the investigators to quantitate the number of cells that migrate to the fracture site, she says.

“What we want to do in the long term is to engineer these cells with growth factors that promote cartilage formation and fracture healing—to combine stem cell therapy with gene therapy,” Spagnoli says.

For mesenchymal and other stem cells, the only way the research will eventually generate therapies “is if we have ways to follow cells after they’re put into humans,” says Sanjiv Sam Gambhir, M.D., Ph.D., director of the Molecular Imaging Program at Stanford University. “If you label these cells with a reporter gene, they’re permanently tagged—bar-coded—for life. And we can keep finding the status of these cells over time.”

Bioluminescence imaging likely won’t be the strategy to follow stem cells in humans, Gambhir says, but it is extremely valuable as a starting point for small animal studies.

“The technologies that are having the most impact in biological models right now are the optical technologies—because of their relative ease of use and suitability for small animals,” Gambhir says. “Bioluminescence and fluorescence are the main workhorses for solving certain problems before moving to the more complex technologies.”

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