Gene and Stem Cell Therapies Reconstructs Injured Bones

Gazit was the principal investigator and co-senior author of the research study, published in the journal Science Translational Medicine.

More than 2 million bone grafts are performed worldwide each year. They are frequently necessitated by severe injuries involving traffic accidents, war or tumor removal. Such injuries can create gaps between the edges of a fracture that are too large for the bone to bridge on its own. The grafts require implanting pieces from either the patient’s or a donor’s bone into the gap.

“Unfortunately, bone grafts carry disadvantages,” said Gazit, a professor of Surgery at Cedars-Sinai. “There are huge unmet needs in skeleton repair.”

See an animation video that shows the bone-tissue engineering technique developed by Cedars-Sinai investigators.
 
Credit: Gazit Group/Cedars-Sinai

One problem is that enough healthy bone is not always available for repairs. Surgeries to remove a bone piece, typically from the pelvis, and implant it can lead to prolonged pain and expensive, lengthy hospitalizations. And grafts from donors may not integrate or grow properly, causing the repair to fail.

The new technique developed by the Cedars-Sinai-led team could provide a much-needed alternative to bone grafts.

In their experiment, the investigators constructed a matrix of collagen, a protein the body uses to build bones, and implanted it in the gap between the two sides of a fractured leg bone in laboratory animals. This matrix recruited the fractured leg’s stem cells into the gap over two weeks. To initiate the bone repair process, the team delivered a bone-inducing gene directly into the stem cells, using an ultrasound pulse and microbubbles that facilitated the entry of the gene into the cells.

Eight weeks after the surgery, the bone gap was closed and the leg fracture was healed in all the laboratory animals that received the treatment. Tests showed that the bone grown in the gap was as strong as that produced by surgical bone grafts, said Gadi Pelled, PhD, DMD, assistant professor of Surgery at Cedars-Sinai and the study’s co-senior author.

“This study is the first to demonstrate that ultrasound-mediated gene delivery to an animal’s own stem cells can effectively be used to treat nonhealing bone fractures,” Pelled said. “It addresses a major orthopedic unmet need and offers new possibilities for clinical translation.”

The study involved six departments at Cedars-Sinai, plus investigators from Hebrew University in Jerusalem; the University of Rochester in Rochester, New York; and the University of California, Davis.

“Our project demonstrates how scientists from diverse disciplines can combine forces to find solutions to today’s medical challenges and help develop treatments for the patients of tomorrow,” said Bruce Gewertz, MD, surgeon-in-chief and chair of the Cedars-Sinai Department of Surgery.

Research reported in this publication was supported by grants from the California Institute for Regenerative Medicine under award number TR4-06713, the National Institutes of Health under award numbers R01CA112356 and P30AR069655, the IDF Medical Corps and the Milgrom Family.

Competing interests: Gadi Pelled, Dan Gazit and Zulma Gazit are shareholders in GamlaStem Medical Inc., which did not provide funds for this study. A patent application related to the study’s findings is pending.