Stem cells, gene therapy and allograft applications show promise for treating orthopaedic conditions

Recent advances in gene therapy, stem cells and other promising applications are offering new hope for patients and helping orthopaedic surgeons provide state-of-the-art treatment for various frame-related conditions.

During a briefing today at the American Academy of Orthopaedic Surgeons' (AAOS) 73rd Annual Meeting, a panel of orthopaedic surgeons and members of the Orthopaedic Research Society (ORS) 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 encouraging techniques is a novel form of adult stem cell therapy for broken bones. Stem cell therapy is performed in lieu of the classic "autograft" technique, used on patients with fractures that are not healing properly. It is not uncommon for bones that are severely injured to heal slowly. Common causes of injury can range from a simple fall to high- energy injuries like car accidents or gunshot wounds. Many patients in these situations undergo multiple reconstructive operations that often require a bone graft, or autograft. Autografts require an incision over the pelvis area to remove some of the patient's own pelvic bone, which is then transferred to the site of the fracture. Such an incision can be quite painful and may be complicated by infection, nerve damage, chronic pain and an unsightly scar. Stem cells offer an effective and less painful alternative to treat simple and complex fractures, particularly those that require additional time to fully heal.

Matthew L. Jimenez, MD, an orthopaedic surgeon at Illinois Bone and Joint Institute, Morton Grove, Ill., is experimenting with adult stem cells to potentially accelerate bone healing and avoid causing patients further discomfort from the self-donation process. Enriching donated bone with a patient's own stem cells, Dr. Jimenez replaces the damaged bone with the stem cell-rich bone. These new cells have the ability to replace the injured portions with new bone.

"The beauty of these adult stem cells is that they can turn into almost any kind of cell, including bone cells and vascular cells," said Dr. Jimenez, one of only a handful of surgeons in the world performing the investigational surgery. "The surgeries we've conducted thus far have had promising results, and to-date, the patients are doing well."

Dr. Jimenez still considers autografts the "gold standard" for bone injuries, but said 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 cutting-edge technique with the potential to mend damaged bones and tissues while sparing patients from undergoing multiple surgeries. Regis J. O'Keefe, MD, PhD, professor of orthopaedics and director of the Center for Musculoskeletal Research at the University of Rochester (NY) Medical Center and treasurer of the ORS, said 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 is that the structural donor bone grafts remain dead, and will fracture in up to 30-40 percent of the cases, Dr. O'Keefe explained. But by placing genes with the ability to induce bone formation onto the surface of a dead bone, the genes provide signals to tissues surrounding the bone and bring it back to life. The resurrected bone is then able to grow and thrive.

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. Dr. O'Keefe hopes further research will uncover alternative delivery methods that do not require the use of viruses.

Currently only two clinical trials are using gene therapy for musculoskeletal applications. Both trials involve introducing genes into cells to counteract proteins that cause inflammation in conditions like rheumatoid arthritis.

"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 can even be used to prevent human diseases from occurring," said Dr. O'Keefe. Development of this approach can lead to a "designer medicine" whereby individualized treatments could be used to prevent debilitating musculoskeletal diseases such arthritis and osteoporosis.

Gary E. Friedlaender, MD, uses donated bone (allografts) in orthopaedic surgery and stressed "the future is already here." Dr. Friedlaender, orthopaedic surgeon and department of orthopaedics chair at Yale University School of Medicine, New Haven, Conn., said allografts can be used to replace diseased or injured bone, tendon and even cartilage. Ligament allografts are often used for sports-related injuries to repair or replace the anterior cruciate ligament in the knee. Some bones like 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," Dr. Friedlaender advised. "Needing to use a patient's own tissue or bone for reconstruction can increase their hospital stay and prolong rehabilitation."

Orthopaedic surgeons are already adept at replacing damaged bone and have begun to successfully transplant cartilage and tendons. Dr. Friedlaender predicts that the potential to also transplant muscle and nerves is in the not-too-distant future. Getting the body to accept donated bone is still somewhat of a challenge, but has been largely overcome. The use of allografts to better serve our patients can only become more widespread if additional bone and cartilage is donated. Dr. Friedlaender stressed this will happen once the public knows that patients truly are in need of these generous gifts and are aware that the science really does work now and, with additional funded research, will work even better in the future.

An orthopaedic surgeon is a physician with extensive training in the diagnosis and non-surgical as well as surgical treatment of the musculoskeletal system, including bones, joints, ligaments, tendons, muscles and nerves.

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