Regenerative medicine for orthopedic conditions (Proceedings)

Soft tissue injuries and osteoarthritis are common conditions afflicting active dogs due to the repetitive forces placed on the joints. Microtrauma to the tendons, ligaments, and the articular surfaces of joints can occur, creating an environment for osteoarthritic development. Once the degenerative cascade of this condition is initiated, its progression can be insidious. Therapies for this debilitating condition have focused on treating the symptoms or slowing the progression of the disease. Regenerative and stem cell thearpy may not only treat symptoms and slow the disease but could help to induce repair of the underlying damage that initiated this cascade. Regenerative medicine technology gives new hope for extending the careers and improving the quality of life of the canine athlete.

Almost all veterinary research has focused on adult stem cells, specifically mesenchymal stem cells, derived from bone marrow (BM-MSC) or adipose tissue (AD-MSC). Veterinary research into the use of regenerative cells and adult stem cell therapy began just this decade. Dr. Roger Smith, of the Royal Veterinary College in England, helped pioneer the movement by developing a technique in 2002 for extracting stem cells from a horse's own bone marrow, growing them in a laboratory for about three weeks, and then injecting them into the injured limb. Meanwhile, in the United States, veterinarian Robert Harman was also developing a therapy for equine orthopedics, using regenerative cells and stem cells extracted from the fat tissue of the horse. His California-based company, Vet-Stem, has been offering the treatment since 2003. Since then more than 2,000 horses have had this therapy with cells processed by Vet-Stem. Conditions treated include tendon and ligament injuries, both acute and chronic, osteochondral defects and osteoarthritis. Multiple studies confirmed efficacy with the majority of horses treated returning to full performance level following treatment.

In dogs, the stem cells and other regenerative cells are obtained from subcutaneous adipose tissues. Adipose tissue is a preferred source in dogs for several reasons including ease of access, high yielding mesenchymal stem cell count as compared to bone marrow, and the fact that it is a renewable source. The cells isolated from the adipose tissue not only include the mesenchymal stem cells but endothelias progenitor cells, pericytes, immune cells, fibroblasts and other growth factor-secreting bioactive cells. The stem cells along with this mix of other regenerative cells are injected directly into the injured tissue, joint and/or intravenously. Because these cells are always obtained from the intended recipient, the risk of rejection and disease transmission is eliminated.

In 2005, Vet-Stem and selected clinics began treating dogs with tendon and ligament injuries and osteoarthrits. Results of the first peer-reviewed, double-blinded, multicenter study for canine osteoarthritis using regenerative and stem cells appeared in Veterinary Therapeutics (Winter 2007 Vol 9, No 4) and demonstrated decreased discomfort and improved function ability in patients that received this therapy. A second study evaluated the use of regenerative and stem cells for use in dogs with clinical signs of chronic osteoarthritis of the elbow. Patients were assessed for lameness, pain on manipulation, range of motion, and functional disability using a numeric rating scale at baseline and specified intervals up to 180 days after treatment. Statistically significant improvement in outcome measures was demonstrated. See Veterinary Therapeutics, Fall 2008 Vol 9, No 3 for the details of this study.

The mechanisms by which these regenerative cells initiate change within the body are complex. MSCs decrease pro-inflammatory and increase anti-inflammatory mediators. MSCs are activated to become immunosuppressive by soluble factors and in turn secrete soluble factors that inhibit T-lymphocyte activation and proliferation. MSCs secrete bioactive levels of cytokines and growth factors that support angiogenesis, tissue remodeling, differentiation, and antiapoptotic events. The cytokines and growth factors secreted by the MSCs can also assist in neovascularization. MSCs demonstrate a diverse plasticity and are able to migrate to sites where needed. Specifics of the functionality of MSCs are detailed in many studies which are discussed on Vet-Stem's website (http://vet-stem.com).

Presently regenerative medicine is being used to treat canine osteoarthritis and canine immune mediated rheumatoid arthritis. The goal of therapy for the canine athlete is to not only to improve comfort but return these athletes to performance level.

This presentation will focus on its use in dogs for the following injuries and disease processes:

     • Medial Shoulder Instability (MSI)

     • Traumatic Fragmented Medial Coronoid Disease ("Jump Down Syndrome")

     • Supraspinatus tendinopathy

     • Cranial Cruciate Ligament Insuffiency

     • Achilles tendon injury

     • Osteoarthritis