A Better Way to Build Bones

Senior citizens and combat soldiers don’t usually have much in common—unless the topic is bone injuries. Among both groups, mending serious skeletal injuries—whether caused by a blast or a common fall—is a costly, complicated challenge. A team of researchers at the New York University Polytechnic School of Engineering, NYU School of Medicine, and Stanford University School of Medicine has received a $1.1 million grant from the U.S. Veterans Health Administration’s Office of Rehabilitation Research and Development to pioneer a novel approach to harnessing the body’s own chemical signals to speed bone regeneration and improve repair.

Alesha B. Castillo, an assistant professor of mechanical and aerospace engineering and orthopaedic surgery at New York University, explained that when bones sustain damage and tissue loss, the body mobilizes an intricate system of chemical signaling to recruit bone-generating stem cells to the site of the injury. As people age, or when damage is especially severe—as combat injuries often are—the quantity of stem cells at the site of the injury is usually inadequate to facilitate full repair, and the chemical signals that should trigger a rush of stem cells to the injury are less effective.

The standard of care in such cases involves harvesting a patient’s stem cells from another part of the body and transplanting them to the injured area, as well as physical exercise because mechanical loading also stimulates osteogenesis.

Castillo and her collaborators, Philipp Leucht, an assistant professor in the Departments of Orthopaedic Surgery and Cell Biology at the NYU School of Medicine, and Jill A. Helms, a professor of surgery at Stanford University School of Medicine, are taking a different approach, exploring the potential for amplifying the body’s signaling system for recruiting bone-forming stem cells to injured areas.

Their work will focus on a single stem-cell recruitment factor found in connective tissue and bone cells, CXCL12 and its receptor, which they hypothesize play key roles in promoting osteogenesis, both in response to injury as well as mechanical stress. Through experiments using genetically modified mice, the team hopes to better define the role of CXCL12 in osteogenesis following mechanical loading as well as its role in bone repair in response to injury. The researchers also plan to explore whether local delivery of CXCL12 can augment the body’s own natural response to bone injury and improve bone repair.

Castillo and her colleagues will begin work this summer, and the Veterans Health Administration grant runs until 2019. Ultimately, the team hopes to advance this research into higher animal models, including humans.
“If we can mobilize and recruit the body’s own stem cells to aid in repair of serious bone injuries, we would have the basis for a very powerful, next-generation therapy,” Castillo explained. “Between the aging population, who are prone to major hip fractures, and large numbers of wounded veterans with complex blast injuries, the promise of a non-invasive therapy that can harness the native signaling pathways to help bones heal better is extremely exciting.”