It’s been more than 30 years since scientists discovered bone morphogenetic proteins (BMPs), molecules that spur bone production. After much experimentation, tests in people show that BMPs can regrow missing or damaged bone. Some severely injured bone does not respond to this therapy, however, because BMPs need a foundation of living cells to stimulate bone formation.
Using rats and mice as models, researchers at the University of Michigan School of Dentistry in Ann Arbor have now devised a gene therapy that delivers cells making both BMPs and bone itself. The study suggests a new line of treatment for hard-to-repair fractures or degenerated bone, both of which would otherwise require that surgeons transfer, or graft, bone or bone marrow from one part of the body to another, says study coauthor R. Bruce Rutherford, a dental scientist at Michigan.
Rutherford and his colleagues knew that BMPs injected into odd places, such as skin or muscle, could induce these tissues to make bone. They took skin cells from rats and combined them in a laboratory dish with a genetically engineered adenovirus to which the researchers had added the gene for a BMP family member called BMP-7. Although the virus can’t replicate it, it infects the cells and induces some of them to produce BMP-7 and others to take on the role of bone-building cells.
Rutherford and his colleagues added the genetically engineered cells to a mixture of protein-rich foam, then applied it to the heads of six rats that had had the tops of their skulls removed. The therapy spurred bone formation so well that 90 percent of the missing skull bone grew back within a month.
“The rapidity with which it filled in was quite surprising to me,” Rutherford says. Six untreated rats with similar injuries re-grew very little bone, the scientists report in the May 20 Human Gene Therapy.
In another BMP-7 experiment, human gum cells treated with the virus in a lab dish launched bone growth in 30 mice.
In both experiments, the virus-infected cells stopped making BMP-7 after 2 to 3 weeks. It’s not clear what ends the process, Rutherford says.
The study “represents a new approach for BMPs,” says Pamela G. Robey of the National Institute of Dental and Craniofacial Research in Bethesda, Md. “There are many [patients] that BMPs by themselves don’t work on.”
These include people whose broken bones become infected or are heavily scarred, says George H. Rudkin, a plastic surgeon at the University of California, Los Angeles School of Medicine.
The gene therapy might also help cancer patients in whom bone has been removed surgically or has been weakened by radiation treatment, which diminishes the number of bone-making cells and limits blood supply to the few remaining, Rudkin says.
The scientists are trying to reduce the need for bone grafts because the procedure causes considerable discomfort and can lead to infection. The researchers next plan to apply the experimental gene therapy to broken thighbones in rodents.