up on fat, researcher finds unlikely treatment
Fractures may someday be healed with fat
By KRISTA CONGER
Certain types of cells from fat tissue can repair skull defects
in mice, say researchers at the medical center. Because this type
of healing process does not depend on the use of embryonic stem
cells or gene therapy, it may one day allow doctors to use a
patient's own unmodified cells as building blocks to heal
fractures, replace joints, treat osteoporosis or correct defects in
bone growth or healing.
"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 the School of Medicine, is the senior
author of the research, published in the May issue of Nature
"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 been investigating the special
qualities of the fat-derived cells, which are isolated from fat
pockets under the skin of juvenile or adult animals, for several
years. 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
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
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
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 to figure 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
The work was supported by a grant from the Oak Foundation and the
National Institutes of Health.
the court to the OR, Longaker plays serious ball (3/13/02)
solve mystery behind skull plate fusion (4/16/03)