Cedars-Sinai Researchers May Revolutionize How Orthopaedic Injuries Are Treated
Jan 15, 2020 Cedars-Sinai Staff
Work being done at Cedars-Sinai may revolutionize how severe orthopaedic injuries are treated. By harnessing the power of resident stem cells, gene therapy and ultrasound, researchers are testing the possibility of helping the body grow new bone after complex or catastrophic damage. The method could be life-altering for patients with such injuries.
Zulma Gazit, PhD, and her colleagues Dan Gazit, PhD, DMD, and Gadi Pelled, PhD, DMD, see extraordinary promise in the approach they're testing with the help of grants from the National Institutes of Health and the Department of Defense.
"We're doing this work because we want to spare people from amputations, pain and prostheses. I believe that one day this will be a standard treatment."
"We're looking at bones with complex fractures, or that have been shattered and can't be repaired in conventional ways," says Zulma Gazit, associate professor of Surgery and co-director of the Skeletal Regeneration and Stem Cell Therapy Program at Cedars-Sinai. "That type of damage can be caused by violent accidents, and for military personnel it can happen on the battlefield. Right now, patients with the most serious orthopaedic injuries don't have a lot of options and really suffer," she adds. "Sometimes the limb needs to be amputated because the fracture won't heal and the prostheses or plates will not last in the long term. We want to prevent that."
While this has not yet been tested in humans, results in animal models are encouraging. The idea is to help the body grow bone, or as Gazit describes it, "helping the body from the inside." The process would consist of three key steps. First, a scaffold made mainly of collagen would be implanted in the area where the shattered bone was cleaned out. Second, the patient would return approximately two weeks later and receive an injection of DNA that specifically encodes for bone formation; by then, resident stem cells would have started to migrate to the scaffolding. Third, ultrasound energy would be applied to the area, opening up pores in the cells, helping pull the DNA into the cells. Once the ultrasound energy is turned off, the pores would close—trapping the DNA inside.
More on the research at the Gazit Lab at Cadars-Sinai
The research is groundbreaking because it uses resident stem cells without the long and laborious process of growing them outside the body. It enlists the body's own capabilities to foster healing from orthopaedic injuries.
The investigators, who are experts in skeletal tissue regeneration, first demonstrated the treatment's efficiency in a 2017 animal study published in Science Translational Medicine, which found the approach successful in regrowing new shinbone in just eight weeks. The team applied the same approach to rapidly heal a massive ligament tear in the knee joint in a study published in Molecular Therapy.
"We're doing this work because we want to spare people from amputations, pain and prostheses," says Gazit. "I believe that one day this will be a standard treatment."