A Cedars-Sinai team of researchers led by principal investigator Dan Gazit, PhD, DMD, has been awarded a $5.18 million grant from California's stem cell research agency to advance stem cell technologies in segmental bone defects, a complex medical problem caused by large portions of bone tissue loss.
The research team will use the grant from the California Institute for Regenerative Medicine to develop a novel approach to treat segmental bone defects without grafting bone. Stem cells will be recruited to the fracture site using a collagen matrix and then a bone-forming gene will be directly delivered to the stem cells using an ultrasound pulse. If successful, researchers will be able to proceed to clinical trials.
Bone tissue, which provides major structural and supportive connective tissue to the body, can be lost due to cancer or trauma. When the edges of a fracture are close to each other, bone repair cells are capable of healing the injury. However, when a large piece of bone is missing, these cells cannot bridge the necessary gap for healing, resulting in the need for bone grafting — the current gold-standard therapy.
Bone grafting can be complicated because healthy bone, typically from the pelvis, is not always available for harvest. In the lab, Cedars-Sinai researchers have shown an alternative approach by modifying stem cells already residing in fracture sites.
"We believe that segmental bone defects could be repaired by recruitment of stem cells to the bone defect site, followed by direct gene delivery," said Gazit, who directs his own Skeletal Regeneration and Stem Cell Therapy Laboratory within the Department of Surgery, the Skeletal Program in the Regenerative Medicine Institute and the Molecular and Micro Imaging Core Facility within the Imaging Core. "Building on this science, ultrasound will be used to further amplify direct gene delivery to bone defects."
"This translational project has the potential to generate rapid healing of segmental bone fractures and therefore significantly decrease patient hospitalization, loss of working days and significant healthcare costs in the future," said Clive Svendsen, PhD, director of the Cedars-Sinai Regenerative Medicine Institute. "In addition, this therapeutic intervention could possibly be repeated several times when needed in order to deal with severe cases of bone loss."
Gazit, who is overseeing a large collaborative group that spans different departments and institutions, will work in collaboration with several leading Cedars-Sinai experts, including co-principal investigator, Hyun Bae, MD, medical director and director of education at the Cedars-Sinai Spine Center and an orthopedic spine surgeon, Zulma Gazit, PhD, Wafa Tawackoli, PhD, Gadi Pelled, PhD, DMD, and Dmitriy Sheyn, PhD.
"This research is a prime example of collaboration among leading scientists, bringing scientific implications directly to patients," said Bruce Gewertz, MD, surgeon-in-chief, chair of the Department of Surgery, vice president for Interventional Services, vice dean of Academic Affairs and the H & S Nichols Distinguished Chair in Surgery.
Researchers discover how mutations disrupt protein splicing and cause disease