Patient's own stem cells used to grow facial bone
29 October 2009
In a first-of-its kind procedure, stem cells taken from the
fat tissue of a 14-year-old boy were combined with growth protein and
donor tissue to grow viable cheek bones in the boy.
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 difficult.
"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
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
"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
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.
The photos at top left and right show 14-year-old Brad
Guilkey a week before his surgery and a few months post surgery.
Side-by-side images of CT scans taken before and after surgery reveal a
noted absence of zygomatic (cheek) bone structure on Brad's face (bottom
left); and the presence of healthy, dense bone structure a few months
following the May 28 procedure (bottom right).
Photo credit: Cincinnati Children's Hospital
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
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
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
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
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 eye injury.
"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."