Stem cell treatment may become option to treat nonhealing bone fractures

The results are being presented at The Endocrine Society's 93rd Annual Meeting in Boston.

A deficiency of fracture healing is a common problem affecting an estimated 600,000 people annually in North America, according to the principal investigator, Anna Spagnoli, MD, associate professor of pediatrics and biomedical engineering at the University of North Carolina at Chapel Hill.

"This problem is even more serious," Spagnoli said, "in children with osteogenesis imperfecta, or brittle bone disease, and in elderly adults with osteoporosis, because their fragile bones can easily and repeatedly break, and bone graft surgical treatment is often not successful or feasible"

Fractures that do not heal within the normal timeframe are called non-union fractures. Using an animal model of a non-union fracture, a "knockout" mouse that lacks the ability to heal broken bones, Spagnoli and her colleagues studied the effects of transplanting adult stem cells enriched with IGF-I. They took mesenchymal stem cells (adult stem cells from the bone marrow) of mice and engineered the cells to express IGF-1. Then they transplanted the treated cells into knockout mice with a fracture of the tibia, the long bone of the leg.

Using computed tomography (CT) scanning, the researchers showed that the treated mice had better fracture healing than did control mice either left untreated or treated only with stem cells. They found that the stem cells enriched with IGF-I became bone cells and helped the cells in the broken bones to repair the fracture, speeding the healing. Compared with controls left to heal on their own, treated mice had more bone bridging the fracture gap, and that new bone was three to four times stronger, according to Spagnoli.

"More excitingly, we found that stem cells empowered with IGF-I restored the formation of new bone in a mouse lacking the ability to repair broken bones. This is the first evidence that stem cell therapy can address a deficiency of fracture repair," she said.

This success in an animal model of fracture non-union, Spagnoli said, "is a crucial step toward developing a stem cell-based treatment for patients with fracture non-unions."

"We envision a clinical use of combined mesenchymal stem cells and IGF-1 similar to the approach employed in bone marrow transplant, in which stem cell therapy is combined with growth factors to restore blood cells," she said. "I think this treatment will be feasible to start testing in patients in a few years."

IGF-I is approved for treatment of children with a deficiency of this hormone, causing growth failure.

The National Institutes of Health supported this study through a NIDDK-NIH R01 grant.