Emerging technologies could affect sports medicine

Stem cells and gene therapy are promising, but much more in vivo data is ne

Issue: October 2003

There are a number of emerging technologies in sports medicine, but despite their promise, many do not have the basic science, pre-clinical and clinical trials needed to demonstrate their safety and efficacy.

“We’ve been working really hard on mechanical factors for the last 20 years, and we think we still have to keep working hard, especially to get in vivo data, but there are other things such as stem cell matrices and computer-assisted surgery that could be of interest in our practice,” Freddie H. Fu, MD, said at a symposium on emerging technologies in sports medicine.

Fu, chair of the department of orthopedic surgery at the University of Pittsburgh Medical Center (UPMC), moderated the symposium at the American Orthopaedic Society for Sports Medicine 29th Annual Meeting.

The limited healing capacity of ligaments and cartilage, as well as problems with muscle injuries and delayed fracture healing, indicate the potential for improving the biological healing process. But technologies such as stem cells, gene therapy and tissue engineering are still mostly at the preclinical stage. “I don’t think that we have enough agreement at this point to tell us exactly where to go.”

Tissue engineering approaches seek to manipulate cellular and biomechanical mediators to affect protein synthesis and improve the formation of tissue that is biomechanically, biochemically and histomorphologically similar to normal tissue, Fu said.

For tissue engineering approaches to work, the carrier matrices used to deliver them must be effective. They must be porous to allow for cell migration, adhesive to allow for cell attachment, elastic for biomechanical stability, biodegradable and biocompatible. A number of matrices have been developed, including protein-based polymers like fibrin and collagen; carbohydrate-based polymers like polylactic acid and polyglycolic acid; artificial polymers like Dacron and hydroxyapatite; and combination polymers.

In experiments, the feasibility of gene therapy has been demonstrated in the repair of ligaments, the meniscus, articular cartilage and the synovial tissue of the knee joint. Viral and non-viral vectors can be used to deliver genetic material, but viral vectors are the most efficient.

Commonly used viruses include adenovirus, adeno-associated virus, retrovirus and herpes simplex virus. But safety is a key issue, Fu said. “How can we assure clinicians who are concerned about safety that we can control gene and stem cell expression?”

Safety concerns

These approaches receive a great deal of media attention, but not all of it is positive. The death of an 18-year-old patient during a gene therapy trial at the University of Pennsylvania in 2000 drew national attention. “These things that we do have a cost and an effect.”

But there is good news as well. In a pilot study, the first FDA-approved gene therapy trial for a nonlethal condition, researchers at UPMC sought to prevent the destruction initiated by interleukin-1 (IL-1) in postmenopausal women with end-stage rheumatoid arthritis of the hand. The joints of these women contained high levels of IL-1, a cytokine that is in large part responsible for the thickening of the synovium, joint erosion and inflammation that leads to joint cartilage breakdown.

Researchers found they could effectively and safely incorporate a gene into synoviocytes to initiate the production of a blocking protein, interleukin-1 receptor antagonist. A phase II study is now underway at Harvard University.

That and other preclinical and clinical work is progressing, Fu said. Stem cells derived from muscle tissue have been identified and tissue engineering approaches are currently being developed to repair, reconstruct, regenerate or replace musculoskeletal tissues. “I’m sure that we can use all this stem cell technology, whether it’s adult stem cells or embryonic stem cells, to form ligaments, cartilage and bone.”

Imaging advances

Advances in imaging for sports medicine are also promising. Conventional imaging is limited by its inability to directly visualize articular cartilage and menisci, and magnetic resonance imaging provides diagnostic advantage over clinical examination only in selected cases.

“We have to look at new technologies, at things like optical coherence tomography (OCT). This is an infrared technique used by ophthalmologists to look at the cornea, and this same technique can be used to image articular cartilage,” Fu said. OCT provides real-time cross-sectional imaging of articular cartilage and detects gaps that are invisible to the arthroscope.

For more information:

Fu F, Musahl V. Emerging technologies in sports medicine: overview. Presented at the American Orthopaedic Society for Sports Medicine 29th Annual Meeting. July 20-23, 2003. San Diego.