БиоПро Выбор потребителя 2018 #07

Stem cells can help correct jaw bone defects

Scientists have succeeded for the first time in growing a jaw along with joints from pig stem cells. The researchers plan to soon use the resulting bone as a graft in clinical trials on patients with severe birth defects.

It is almost impossible to replace the jawbone in people suffering from congenital defects or accidental injuries. Curved, with a complex structure, it ends with a joint covered with a layer of cartilage. Both parts have to withstand enormous pressure when chewing.

“It is one of the most loaded bones in the human body”, – said Gordana Vunjak-Novakovic, a professor of biomedical engineering, medicine and dental medicine at Columbia University in New York.

In a paper published in Science Translational Medicine, she and her colleagues reported an astonishing success: they were able to grow jaw bones along with joints from pig stem cells. Clinical trials are planned to begin in the near future.

The researchers hope that someday this approach can be used to grow and transplant other bones and joints, including the knees. However, even if this strategy works, it will be years before it is possible to create new joints or jaw bones from patients’ own cells that need transplants.

Dr. Sidney Eisig, chair of the department of dentistry at Columbia University Hospital, said the work had begun in part because of frustration with the options available to surgeons like him.

If a jaw bone replacement is needed, grafts from other parts of the patient’s body may not be practical. As a rule, they are not correct shaped – most of the bones are straight and relatively flat, and the jaw bones are curved.

“It is hard to take a straight piece of bone and put a curve on it”, – Dr. Eisig said. “In addition, there may be insufficient quantity, and taking grafts requires a second surgical site on the patient”.

Currently, metal prostheses are used to replace the temporomandibular joint (TMJ), to which the jaw is attached. This method is applicable in cases of severe arthritis, in which the TMJ is destroyed, and patients can hardly open their mouths, while experiencing severe pain.

However, these prostheses have not been tested in long-term trials to study the side effects that may develop over time, said Dr. Tara Aghaloo, a maxillofacial surgeon at the University of California, Los Angeles, who was not involved in the study.

Surgeons are faced with a difficult choice: can these prostheses be installed in young people with severe arthritis? In addition, a significant number of patients suffer from joint metal allergy.

“I always thought there has to be a better way to do this”, – Dr. Eisig said.

About 10 years ago, he noticed a scientific article by Dr. Vunjak-Novakovic in which she reported the creation of the human TMJ condyle (a relatively small piece of bone that articulates with the joint fossa) from human fat stem cells.

Dr. Eisig went to Dr. Vunjak-Novakovic’s laboratory and convinced her to create a curved bone along with the joint, in a larger animal. They decided that a pig would be ideal – these animals have jaw joints similar to those of humans.

Scientists decided to use cow bones as a kind of scaffolding. To give the required shape to the bones, from which the cells of the cows were previously removed, they were processed on a computer-controlled device. The resulting scaffolds were individual for each test animal.

The mesenchymal stem cells (MSCs) needed to create the jaw were isolated from the pigs’ own fat obtained by liposuction. Scientists have divided MSCs into two groups. The development of the first group was stimulated for bone formation. These cells were placed inside the scaffold. The differentiation of the second group was directed by researchers to the development of cartilage tissue. The cells were seeded on the surface of the scaffold.

After five weeks, the bone-cartilage grafts were ready. The team sent the bones to Louisiana State University, where staff transplanted them into pigs that had their jaws removed.

“As soon as they woke up, they started to move around and started to eat”, – Dr. Vunjak-Novakovic said.

The fact that the pigs were able to eat immediately was encouraging. Six months later, researchers euthanized the animals and examined the transplanted jaws. The cow bone carcass had been reabsorbed into the pigs’ bodies. The team also found that the new jaw bones were indistinguishable from those in the animals that had originally been there.

Scientists plan to soon conduct clinical trials, which will involve six patients with a shortened lower part of the face and open bite. Surgeons will rotate the jawbone and close the gap by implanting the grown bone, thus lengthening the face so that patients can close their mouth.

Dr. Eisig said he had waited decades for this kind of progress.

“It’s preliminary, but it is very exciting”, – he said. “I’m glad it is happening while I’m still practicing.”