"These cells are from you, for you and by you," said Lucile Packard Children's Hospital pediatric craniofacial surgeon Michael Longaker, MD. "They are not foreign and they don't express foreign genes. To our knowledge, this is the first time these cells have ever been shown to have a therapeutic effect." Longaker, a professor of surgery at Stanford's School of Medicine, is the senior author of the research, published in the May issue of Nature Biotechnology.
"Fat is a great natural resource," he added. "These cells are not only easily harvested, they grow quickly in the laboratory." In contrast, bone marrow cells and bone cells, both of which can also repair skull damage, grow very slowly outside of the body.
Longaker and his colleagues have spent several years investigating the special qualities of the fat-derived cells, which are isolated from fat pockets under the skin of juvenile or adult animals. They've found that the cells, also known as multipotent cells, can be coaxed in the laboratory to express the genes and characteristics of many other tissue types, including bone, cartilage and muscle cells. But it was not known if these cells are equally versatile within the body.
In the study, researchers implanted the cells, seeded on a bonelike scaffolding, into defects that would not otherwise heal in the skulls of mice. They assessed new bone formation after two and 12 weeks, finding that the fat-derived cells were just as effective as the more finicky bone marrow cells at synthesizing new bone to bridge the defect. In contrast, cells derived from tissue that covers the brain showed no bone growth during the same time period.
The new bone growth began next to the brain, suggesting those cells were sending out bone growth-promoting signals and emphasizing the importance of the local environment in determining cell fate.
"The analogy is one of seeds and soil," said Longaker. "The cells are the seeds, and the soil that enables them to form bone consists of the scaffolding and the signals of neighboring cells."
Because more than 95 percent of the new bone growth was made up of implanted cells, researchers speculate the fat-derived cells either became bone themselves, as they have done in the laboratory, or fused with existing bone-making cells in the host to spur new growth.
If the researchers' findings can be reproduced in humans, they may lead to new, more effective and biologically gentle ways to promote healing of tricky fractures and skeletal defects.
"After age 2, you don't re-engineer a defect in your skull," said Longaker. "Currently, surgeons use bone grafts from the patient's ribs or split other parts of the skull horizontally to gain enough bone to cover the area. Alternatively, they can rely on plastic or metal inserts. But all of these options can give you problems with infection and healing, and can be invasive and technically difficult."
Other conditions that might benefit from the use of the multipotent cells include joint replacement, spinal fusion, osteoporosis and osteomyelitis, a bacterial infection of the bone.
"As more people are active in sports and live longer, the wear and tear on joints is obvious," said Longaker. "The non-human tissue we use to replace joints may last 10 to 20 years if it's well integrated. Our hope is that we could do better by replacing that with your own tissue. The key to this type of regenerative medicine is to understand the developmental biology of skeleton formation during embryogenesis, and figuring out how to release those same coaching signals in children and adults.
"These cells are readily available, easily expandable and they don't require gene therapy to work," he added. "In the future we may not have to leave the operating room or the patient's bedside to use cell-based therapies for skeletal regenerative medicine."
The work was supported by a grant from the Oak Foundation and the National Institutes of Health.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.
Lucile Packard Children's Hospital at Stanford is a 256-bed hospital devoted to the care of children and expectant mothers. Providing pediatric and obstetric medical and surgical services and associated with Stanford University School of Medicine, Packard offers patients locally, regionally and nationally the full range of health-care programs and services - from preventive and routine care to the diagnosis and treatment of serious illness and injury. To learn more about Lucile Packard Children's Hospital at Stanford, please visit http://www.