Gene and Stem Cell Therapies May Help Heal Fractures

Jun. 12, 2017

Hani Awad, Ph.D.,​URMC researchers partnered with Cedars-Sinai colleagues on a study that tested a new method for repairing severe fractures in laboratory animals. The new technique combines ultrasound, stem cell, and gene therapies to cue bone to regenerate itself. Researchers believe the technique may someday replace bone grafting as a way to mend severe fractures.

On average, about 100,000 people in the U.S. experience severe fractures that fail to heal each year. The current standard of care for these injuries often involve long hospital stays, repeated surgeries, and still result in long-term disability. 

While bones are usually able to repair themselves in the case of small cracks and fractures, severe breaks and fractures leave too big a gap for bones to fill on their own. In these cases, missing bone may be replaced by bone from another place in patient’s body, which is painful and may cause infection at the donor site, or by a piece of bone from a cadaver, does not always integrate well with the patient’s bone because it is dead tissue.

The new fracture-healing method published in the journal Science Translational Medicine, helped bones regenerate across large gaps in leg fractures of laboratory animals. Hani Awad, Ph.D., professor of Biomedical Engineering and Orthopaedics at the University of Rochester Medical Center, tested the healed fractures in Center for Musculoskeletal Research’s state-of-the-art Biomechanics Lab with the help of Jayne Gavrity, a biomechanical and imaging engineer in the CMSR. According to Awad, the newly formed bone was as strong as the patient’s own bone grafts, suggesting the new procedure could replace the painful grafting procedure.

To heal the fractures, the team filled the fracture gaps with a scaffold of collagen, a structural protein the body normally uses to make bone. Over two weeks, stem cells were recruited to the scaffold in the fracture site. Then the team delivered a gene to the stem cells that would turn them into bone-creating cells. The gene was delivered with the aid of microbubbles that create tiny holes in the stem cell membrane and enable entry of the gene into the cells when they are hit with pulses of ultrasound.

This technique, which improves upon other investigational therapies that are costly, painful, and increase risk of infection and tissue damage near the fracture site, was able to completely heal leg fractures in the laboratory animals in just eight weeks.

Co-senior authors, Dan Gazit, Ph.D., D.M.D., co-director of the Skeletal Regeneration and Stem Cell Therapy Program in the Department of Surgery and the Cedars-Sinai Board of Governors Regenerative Medicine Institute, and Gadi Pelled, Ph.D., D.M.D., assistant professor of surgery at Cedars-Sinai, hope this technique will be useful in humans, but more studies are needed to determine this.

The study was featured in Science Magazine, a publication of the American Association for the Advancement of Science. You can find that article here.  

To read the full study, click here.