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Friday, October 16, 2009

Stem Cells from Fat Used to Grow Teen's Missing Facial Bones

Surgeons report success in first human bone growth procedure using fat stem cells--with no culturing necessary

By Katherine Harmon

stem cell bone growth

NEW BONE: A CT scan of the patient's skull after the stem cell treatment helped him regrow missing cheekbones

stem cell bone growth

BEFORE TREATMENT: A CT scan shows the Treacher Collins syndrome patient, who was born without cheekbones, before the stem cell procedure

Stem cells so far have been used to mend tissues ranging from damaged hearts to collapsed tracheas. Now the multifaceted cells have proved successful at regrowing bone in humans. In the first procedure of its kind, doctors at Cincinnati Children's Hospital Medical Center replaced a 14-year-old boy's missing cheekbones—in part by repurposing stem cells from his own body.

The technique, should it be approved for widespread use, could benefit some seven million people in the U.S. who need more bone—everyone from cancer patients to injured war veterans.

"This is sort of the holy grail for a number of different surgeons," says Jesse Taylor, a surgeon and researcher in the hospital's Division of Plastic Surgery and one of the procedure's lead physicians. The procedure could be used in plastic, orthopedic and neural surgeries, he notes. Some bone tissue had previously been generated from stem cells in the lab, but this marks hope for a surgical solution for those who need additional bone.

"We often find ourselves in the operating room saying, 'Man, I wish we had a little more bone,'" Taylor says. In adult patients plastic and metal have often subbed in, in the absence of bone, but as Taylor notes: "What happens if someone gets a fracture? It's another surgery." In contrast, a natural bone regrown from stem cells should heal on its own. Another alternative, bone transplants—either repurposed from the patient's body or from cadavers—have high rejection and absorption rates, leading to many unsuccessful attempts.

To create the new bones, which have become part of the patient's own skull structure and have remained securely in place for four and a half months, the medical team used a combination of fat-derived stem cells, donated bone scaffolds, growth protein, and bone-coating tissue.

No culturing required
After honing the bone-growth technique in laboratory pigs for more than two years, Taylor and his team were ready to attempt it in a person.

Their first patient was Brad Guilkey, who had been born with Treacher Collins syndrome (TCS), a rare genetic defect, which in Guilkey's case resulted in the absence of some of his facial bones. Guilkey, who was 14 at the time of the surgery, had been born without either zygomatic bone—the two upper cheekbones that protect the eyes and form the normal cheek contours. "We were basically able to make new ones for Brad," says Taylor of the bones. Before the surgery, Guilkey's face sloped slightly inward—and his eyes downward—and a lack of protective bone left his eyes vulnerable, especially when he played his favorite sports, basketball and baseball.

Unlike many other stem cell treatments, such as heart patches, the procedure Taylor and his colleagues used did not require any advance culturing or growth in the lab. The intensive, daylong surgical procedure included every step—from the stem cell harvesting through liposuction to bone implantation.

The group chose fat stem cells over those from bone marrow largely because of the ease of access. "One of the neat things about adipose-derived stem cells is they're very easy to harvest," Taylor says. They also exist in just about the same proportion as bone marrow stem cells, which can be more difficult to obtain.

For the surgery, Taylor and his team shaped donor bone—from cadaver-donated femurs—to resemble zygomatic bones and act as a biological scaffold for the bone to grow on. Mesenchymal stem cells, harvested from Guilkey's fat, and growth-encouraging morphogenetic protein-2 (BMP-2), were injected into holes drilled into the scaffolds. Before implanting the bone sections into Guilkey's face, Taylor and his team wrapped them in periosteum tissue, which covers bone surfaces and was harvested from Guilkey's leg. The surrounding material, especially the periosteum and the growth protein, helped to cue the stem cells to produce bone tissue.

New bones for all?
The new technique may have applications across the board for those who need bone regeneration, but it may not be as successful—or as simple—in every case.

Some of the procedure's effectiveness may be due to Guilkey's youth. "The periosteum, which is probably the most important component, changes as you get older," Taylor says. This membrane, which covers healthy bones, helps to supply bones with blood and nutrients, encouraging growth and healing. So new bone may not generate as quickly in a 70-year-old as someone in his or her teens, he notes. The team is performing tests on pigs of different ages to see how much of a role senescence plays in the growth and healing process.

Overcoming genetic diseases, such as Guilkey's TCS, can be challenging, Taylor notes, as repurposing that person's biological material does not eliminate the mutations that caused a lack of bone in the first place. Although Taylor gives Guilkey's procedure better than a 50–50 chance of long-term success, he remains cautious. "The real proof of the pudding of this concept will be whether it's there in five years," he says. If it is, "that will be really amazing." Other, more traditional bone grafts for similar patients often start to come loose within a few months of the procedure. But, he says, Guilkey's new bones remain "rock steady."

Using the procedure in cancer patients may prove to be the most difficult due to intensive scarring and the fact that the growth protein, BMP-2, is not approved for use in people with cancer. Traumatic injuries will likely be the easiest to fix, provided the patient can wait six months to a year for scars to heal, says Taylor.

Unknown mechanisms
The results from Guilkey's surgery show that culturing stem cells extensively before implanting them might not be the only path to take in developing new stem cell treatments. "We're thinking at this point that that might not be such a great idea—to induce them into becoming something [specific]. Maybe some of these cells need to become something else," Taylor says. To grow bone, the body also needs vascular cells, fat cells and others. So why, Taylor proposes, limit a stem cell implantation to only one kind of cultured, differentiated cell?

The procedure does highlight the vast amount of research that remains to be done. "There's so much we don't know," Taylor says. "And to pretend that we have control over everything is presumptuous." He favors using biological rather than artificial scaffolds. "I try to use as many natural cues and processes as possible," he says. "There's a lot we don't understand mechanistically," so he prefers "putting it in an environment that says, 'Become a bone.'"

Although the approach may sound overly simplistic for Guilkey and at least and two other patients who have undergone the procedure since, it appears to have been successful. "It's primitive, but it works," Taylor says. "Now the onus is on us to figure out why it works."

In the meantime, Taylor says, Guilkey, now 15, has become a lot more outgoing and has even cut his hair short for the first time in his life—rather than try to cover up his face with long locks. Taylor reports that the teen has been able to return to sports and is now dating.