CINCINNATI, Oct. 12 (Reuters) — In a first-of-its kind procedure, physicians have used stem cells taken from the fat tissue of a 14-year-old boy and combined them with growth protein and donor tissue to grow viable cheek bones in the teen.
The new procedure dramatically improves the options surgeons have for
repairing bone deficiencies caused by traumatic injuries – such as those from
car accidents or soldiers wounded in battle – or by disease and genetic
conditions, according to Jesse Taylor, M.D., a surgeon and researcher in the
Division of Craniofacial and Pediatric Plastic Surgery at Cincinnati
Children’s Hospital Medical Center. An estimated 7 million people in the
United States have defects in bone continuity so severe that repair is
"We think this will benefit millions of people who, through traumatic injury
or disease, have significant bone defects," Dr. Taylor explained. "The current
methods we have – like borrowing bone from another part of the body, or
implanting cadaver bone or something artificial – are reasonable alternatives,
but far less than perfect."
Because the body rejects or absorbs implanted donor material, many
reconstructive surgeries can have high failure rates. In procedures where bone
is borrowed from one part of the body to replace another, the corrective
surgery itself can be disfiguring to the person doctors are trying to help.
The new procedure avoids these problems because it uses the patient’s own
cells, Dr. Taylor explained. His team developed the procedure based in part on
scientific research conducted in pigs at Cincinnati Children’s. The operation
is the first to blend and refine several techniques used or under study in
surgical practice for repairing bone deficiencies.
The teenage recipient of the surgery, performed on May 28, has a rare genetic
condition known as Treacher Collins syndrome, which includes underdeveloped or
missing cheek bones. In this case the teenage patient, Brad Guilkey of
Cincinnati, did not have developed zygomatic bones on either side of his face.
The zygomatic bones form the prominence of the cheek and part of the outer rim
of the eye socket.
The missing bones affected the active teenager’s appearance, but more
importantly put his eyes at increased risk of injury, Dr. Taylor said. The
bones are supposed to surround most of the lower and side areas of the eye
sockets, with a portion protruding toward the ear at the cranial base.
"This bone is critical structurally and acts as a shock absorber for the face,
protecting the eyes and other critical structures in the event of facial
impact," explained Dr. Taylor. "This young man is extremely active, he loves
to play basketball and baseball, and growing new bone in this area of his
craniofacial structure is critically important for him."
Dr. Taylor said the procedure has been successful and, more than four months
after the surgery, computer tomography (CT) scans show the teenager’s cheek
bones have filled in normally with viable bone. The new bone structure
enhances his appearance and improves protection for his eyes. Additional
touchup surgery to the teenager’s eye lids is under consideration to address a
slight downward slant, also characteristic of Treacher Collins syndrome.
During the day-long operation, surgeons used a section of donor bone to craft
what essentially were mineral-based scaffolding implants (known as
allografts), which also served as a growth guide for the new bone. Surgeons
drilled holes in the allografts, which then were filled with mesenchymal stem
cells taken from the patient’s abdominal fat. Also injected into the
allografts was a growth protein called bone morphogenic protein-2 (BMP-2) that
instructs the stem cells to become bone cells called osteoblasts.
One of nature’s roles for mesenchymal stem cells is to become cell types for a
variety of different tissues in the body – including connective tissue and
bone – giving the body a ready reserve of replacement cells as older cells
die. In the surgery, and in the earlier lab experiments involving pigs, the
doctors used BMP-2 to jumpstart nature’s normal process of transforming these
malleable stem cells.
"We only need to use a fairly small amount of bone morphogenic protein to
serve as a cue to tell the mesenchymal stem cells that they’re going to become
bone," explained Donna Jones, Ph.D., a researcher at Cincinnati Children’s and
part of the scientific team that conducted experiments leading to the
procedure. "The actual molecular mechanisms BMP-2 uses to do this are not well
understood, but once we use BMP-2 to start the process, the body’s own
biological processes take over and it produces its own BMP-2 to continue the
Particularly critical to that process is wrapping the donor allograft bone in
a thin membrane of tissue that coats bone surfaces called periosteum. The
periosteum used in this surgery was taken from the patient’s thigh. Periosteum
is important to the body’s normal production of BMP-2, and just as vital to
providing a blood supply to nourish new bone formation.
Drs. Taylor, Jones and their fellow researchers are conducting ongoing studies
into growing mandible bones in pigs. In a research paper being prepared for
peer-review journal publication, they explain the use of the procedure to grow
viable, dense bone in the animals and the duplication of results numerous
times. The researchers worked with pigs because the porcine immune system is
very similar to that of humans, making the animals a good model for simulating
engineered bone growth in people.
Peer-review presentations of results from aspects of the study results have
occurred at national re-constructive surgery conferences – including the
American Association of Plastic Surgeons and the Plastic Surgery Research
Council – and received with great enthusiasm, said Christopher Runyan, M.D.,
Ph.D., a member of the research team at Cincinnati Children’s.
The team also plans additional research projects to test the procedure’s
ability to engineer bones of different lengths and sizes. Drs. Taylor and
Jones said the technology may have the potential to grow almost any bone in
the human body. As for Brad, now 15, and his mother, Christine, they’re just
happy Brad can play sports and participate in other activities without having
to worry about a lack of facial bone making him more susceptible to serious
"Until we had the CT scans before surgery, we had no idea that Brad was
missing the bones that protect his eyes, and that’s very dangerous," said
Christine. "I was nervous about the procedure, but we’re glad we did it and
amazed with the results. The people at Cincinnati Children’s do a great job of
explaining things to you and we have a lot of trust in the doctors and staff."
Additional details about the research and surgery, including photographs and a
video, are available at www.cincinnatichildrens.org/bone-growth.
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