Medical Device Daily Associate

CHICAGO - Recent advances in stem cells, gene therapy and other promising applications are offering new hope for patients and helping orthopedic surgeons provide cutting-edge treatment for various frame-related conditions.

During a press briefing sponsored by the American Academy of Orthopaedic Surgeons (AAOS; Rosemont, Illinois) at the vast McCormick Place Convention Center on Wednesday, a panel of orthopedic surgeons and members of the Orthopaedic Research Society (also Rosemont) discussed how these investigational applications may someday treat a variety of bone, joint and muscle-related conditions more readily than many physicians ever imagined possible.

Among the most interesting techniques discussed was a form of adult stem cell therapy for broken bones.

Stem cell therapy is performed in lieu of the classic autograft technique, currently used on patients with fractures that are not healing properly. And it is not uncommon for bones that are severely fractured to heal slowly. Common causes of injury can range from a simple fall to high-energy injuries such as automobile accidents or gunshot wounds.

According to Matthew Jimenez, MD, an orthopedic surgeon at Illinois Bone and Joint Institute (Morton Grove, Illinois), many patients in these situations undergo multiple reconstructive operations that often require a bone graft or autograft.

He said the patients involved in a 36-patient Phase II safety trial he reported on were “the worst of the worst,“ adding that the six-month data he presented at the AAOS meeting was only on the first seven patients enrolled, although 34 patients have been enrolled and he expects the six-month results for all the patients to be available in a seven-month timeframe.

Jimenez is experimenting with adult stem cells, extracted from a patient's iliac crest, to potentially accelerate bone healing and avoid causing patients further discomfort or problems resulting from the self-donation process required for an autograft.

Enriching donated bone with a patient's own stem cells, Jimenez replaces the damaged bone with the stem cell-rich bone, which has the ability to replace the injured portions with new bone.

The stem cell enrichment process was developed by Aastrom Biosciences (Ann Arbor, Michigan), with Jimenez explaining that Aastrom “proliferates“ the stem cells to regenerate tissue at a fracture site. These regenerative cells are also known as tissue regenerative cells (TRCs).

“The beauty of these adult stem cells is that they can turn into almost any kind of cell, including bone cells and vascular cells,“ he said. Jimenez is one of only a handful of surgeons in the world performing the still-investigational surgery.

He said there have been no adverse events related to the TRCs and that all the bones treated, thus far, have healed by the six-month data point, which he said was remarkable, especially considering this patient population.

Jimenez said he still considers autografts to be the “gold standard“ for bone injuries, but that stem cell therapy - with continued research - shows great promise to speed the healing process and avoid the need for additional operations.

Gene therapy is another promising new technique with the potential to mend damaged bones and tissues while sparing patients from multiple surgeries.

Regis O'Keefe, MD, PhD, professor of orthopedics and director of the Center for Musculoskeletal Research at the University of Rochester Medical Center (Rochester, New York), described how his laboratory works on methods to introduce genes into bone-forming to improve the cells' function and increase bone formation.

One of the concerns with replacing injured bone with donated bone, according to O'Keefe, is that the structural bone grafts remain dead and will fracture in up to 30% to 40% of the cases. But he said that by placing genes that have the ability to induce bone formation onto the surface of a dead bone, the genes provide signals to the tissues surrounding the bone and bring it back to life. The “resurrected“ bone then is able to grow and thrive.

O'Keefe said researchers are working to improve the safety of gene therapy, which involves using a non-disease-causing virus to deposit the gene into a cell. The virus attaches onto the cell's surface and pokes a hole through the membrane to inject the genes into the cell.

O'Keefe said he hopes further research will uncover alternative delivery methods that do not require the use of viruses, such as using “naked DNA,“ or DNA plus a carrier such as a liposome or polymer.

“As we better understand the function of individual genes, we may be able to predict how alterations in the expression of specific genes can lead to disease, or even can even be used to prevent human diseases from occurring,“ said O'Keefe. He added that this approach may lead to “designer medicine“, whereby individualized treatments could be used to prevent debilitating musculoskeletal diseases such as arthritis and osteoporosis.

Gary Friedlaender, MD, an orthopedic surgeon and department of orthopedics chair at Yale University School of Medicine (New Haven, Connecticut), is using donated bone (allografts) to replace diseased or injured bone, tendon and even cartilage.

Ligament allografts often are used for sports-related injuries to repair or replace the anterior cruciate ligament in the knee. Some bones, such as the end of the femur in the thigh, he noted, can only be substituted with donated bone.

“Allografts are safe and effective and don't sacrifice normal bone to repair body parts that are diseased or broken,“ said Friedlaender. “Needing to use a patient's own tissue or bone for reconstruction can increase their hospital stay and prolong rehabilitation.“

While he said that getting the body to accept donated bone has been largely overcome, it remains a challenge in some patients.

Friedlaender also predicted, in the not-too-distant future, the possibility of transplanting muscle and nerves.