In a groundbreaking tissue engineering procedure, doctors in the US used the patient’s own stem cells to help a 14-year old boy with a rare rare genetic condition that left him with underdeveloped and partly missing cheekbones grow new facial bone. They say the successful operation vastly increases the reconstructive surgery options available to patients with facial bone disfigurements, including those who have been in car accidents, soldiers injured in battle, and also patients with inherited diseases.

Doctors at Cincinnati Children’s Hospital Medical Center took stem cells from Brad Guilkey’s fat tissue and combined them with growth protein and donor tissue to help him grow viable cheek bones. Brad, who is now 15, underwent the main surgical part of the procedure earlier this year on 28 May.

Brad has a rare condition known as Treacher Collins syndrome where the zygomatic bones on either side of his face were underdeveloped. The zygomatic bones form the prominence of the cheek and part of the outer rim of the eye socket.

Not having the usual protection of bone around the lower and side areas of the eye sockets not only affected Brad’s appearance, but also put the active teenager at higher risk of eye injury.

Dr Jesse Taylor, a surgeon and researcher in the Division of Craniofacial and Pediatric Plastic Surgery at Cincinnati Children’s told the press that:

“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.”

“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,” he explained.

Brad’s day-long operation appears to have been successful. More than four months after surgery, computer tomography (CT) scans show that his cheek bones filled in normally with viable bone. Not only are his eyes better protected, his appearance is also enhanced, and further touch up surgery is planned to remove the downward slant of the eyes that is characteristic of Treacher Collins syndrome.

During the operation surgeons used a piece of donor bone to make “scaffolding” implants or allografts to guide the growth of new bone. They drilled holes in the allograft and filled them with with mesenchymal stem cells from Brad’s abdominal fat.

Mesenchymal stem cells have the potential to become a variety of cell types, including connective tissue and bone, giving the body a reserve of replacement cells as older cells die. Growth proteins control what happens to them by sending them different signals to become cells for different types of tissue, depending on the body’s needs.

The doctors injected Brad’s cheek allografts with the growth protein bone morphogenic protein-2 (BMP-2), which instructs mesenchymal stem cells to turn into bone cells or osteoblasts.

Taylor said the new procedure vastly increases the surgical options available to help repair bone damage caused by traumatic injuries, for instance those suffered by wounded soldiers and victims of car accidents, as well as patients like Brad whose bone deficiency is caused by disease or a genetic condition.

Estimates suggest some 7 million Americans have some defect in bone continuity that is so severe it is difficult to repair.

As Taylor went on to explain:

“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.”

Also, many reconstructive surgeries using current methods have a high failure rate because they use donor tissue, which the body often rejects. And procedures that use material taken from another part of the patient’s body can often leave them disfigured.

Taylor said the new procedure avoids both these problems by using the patient’s own stem cells. They developed the procedure at first using pigs at Cincinnati Children’s, and found that they could jumpstart the body’s normal process for turning mesenchymal stem cells into bone cells using BMP-2.

Dr Donna Jones, a researcher in the scientific team that conducted experiments leading to the procedure said:

“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.”

“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 transformation,” she explained.

A delicate part of the procedure was the removal of tissue from Brad’s thigh and wrapping it around the donor allograft to generate the thin membrane called periosteum that coats bone surfaces. Periosteum is important for producing BMP-2 naturally in the body and also helps with supplying blood to nourish the new bone.

Brad and his mother Christine are delighted with the surgery. They look forward to Brad being able to resume his sporting and other activities without having to worry about lack of facial bone making him more vulnerable to serious eye injury.

Brad’s mother said it wasn’t until they saw the results of the scan that they realized just how much bone was missing from his face. She said she was nervous about the operation, but they are now glad they took the decision, and she praised the doctors and staff at the hospital, saying they also did a “great job of explaining things”.

Source: Cincinnati Children’s Hospital Medical Center.

Written by: Catharine Paddock, PhD