New Musculoskeletal Regeneration Program represents therapeutic pipeline from biomedical discovery to clinical implementation

The Mayo Clinic Center for Regenerative Medicine recently announced the launch of the Musculoskeletal Regeneration Program. Physicians and scientists in this new program are focused on the repair of diseased or injured tendons, ligaments, cartilage, muscle and bone using advanced stem cell and tissue engineering platforms.

This work involves a multidisciplinary team encompassing orthopedic surgery, sports medicine, physical medicine and rehabilitation, and rheumatology with the common goal to improve the current standard of care. These emerging regenerative technologies, focusing on structural repair and functional restoration, are poised to provide innovative solutions that address unmet patient needs.

Musculoskeletal degeneration and complications from injuries are becoming more prevalent as the population lives longer and participates in rigorous athletic and recreational activities. These tissue defects may immobilize patients, as well as cause inflammation and pain.

This team represents a therapeutic pipeline from biomedical discovery to clinical application that seeks to repair, restore or rejuvenate bone, cartilage and soft tissue structures that are affected by acute injury, chronic degeneration, genetic dysfunction and cancer-related defects.

Mayo researchers will examine musculoskeletal tissue injury and repair using molecular, cellular, tissue and organ-level approaches, including molecular profiling, histology, imaging and biomechanics, to support the integration of new knowledge to improve the diagnosis and treatment of diseases and injuries of the skeleton and its associated tissues.

The Musculoskeletal Regeneration Program is based at Mayo Clinic's campus in Rochester, Minnesota, and led by Mark W. Pagnano, M.D., chair of Orthopedic Surgery. As efforts in the Musculoskeletal Regeneration Program span the full spectrum of discovery, translation and clinical application, Andre J. van Wijnen, Ph.D., will serve as associate director, discovery; Christopher H. Evans, Ph.D., director of Mayo Clinic's Rehabilitation Medicine Research Center, will serve as associate director, translation; and Jay Smith, M.D.,  vice chair of Physical Medicine and Rehabilitation, will serve as associate director, clinical application.

Listed below are a few of the current projects led by staff from Mayo's Department of Physical Medicine and Rehabilitation.

Slowing or reversing muscle loss via myostatin inhibition

Lead investigator: Nathan K. LeBrasseur, M.S., Ph.D., Physical Medicine and Rehabilitation, at Mayo Clinic's campus in Rochester, Minnesota

Dr. LeBrasseur and colleagues are exploring new ways to increase muscle mass and improve strength, physical function and whole-body metabolism, and reduce frailty related to aging and chronic disease. This research focuses on the growth and differentiation factor-8 (GDF-8), also known as myostatin, which functions as a potent negative regulator of muscle growth. Mayo Clinic researchers are examining whether myostatin can serve as a mediator of sarcopenia or cachexia and as a therapeutic target. Dr. LeBrasseur's team has just developed a novel assay to specifically and accurately measure myostatin and related proteins in a small volume of human blood. And the team is participating in a multicenter clinical trial of a myostatin receptor antagonist in people age 70 and older with sarcopenia and reduced mobility.

Autologous culture-expanded adipose-derived mesenchymal stromal cells for knee osteoarthritis

Lead investigator: Jay Smith, M.D., vice chair of Physical Medicine and Rehabilitation at Mayo Clinic, and associate director, clinical application, for the Musculoskeletal Regeneration Program

According to Dr. Smith, this will be the first trial at Mayo Clinic to examine the safety and efficacy of culture-expanded stem cells for the treatment of knee osteoarthritis, a problem affecting millions of Americans. This trial represents a critical step in developing next-generation cellular therapies that can be delivered in the clinic. Currently, Mayo Clinic offers bone marrow concentrate (BMC) to patients with refractory arthritis who want to avoid or delay surgical intervention. BMC contains a variety of potentially beneficial cells (including stem/stromal cells) as well as bioactive factors.

Use of gene therapy for knee osteoarthritis, Phase I clinical trial

Lead investigator: Christopher H. Evans, Ph.D., director, Mayo Clinic Rehabilitation Medicine Research Center, and associate director, translation, for the Musculoskeletal Regeneration Program

Approximately 27 million Americans have osteoarthritis, and the disease is incurable, largely untreatable and the major cause of disability among the elderly. The Mayo Clinic research team plans to use a viral vector to introduce an anti-arthritic gene into the knee joints of patients with osteoarthritis. In separate studies, gene therapy is being developed to regenerate cartilage and heal bone.

Use of platelet-rich plasma for the treatment of hip osteoarthritis

Lead investigator: Jacob L. Sellon, M.D., Physical Medicine and Rehabilitation and Sports Medicine Center at Mayo Clinic's campus in Rochester, Minnesota

This prospective investigation will compare the effects of cortisone versus platelet-rich plasma (PRP) injections for the treatment of hip osteoarthritis. PRP, which is generated from the patient's own blood, contains a variety of anti-inflammatory and regenerative substances and has demonstrated some promise in the treatment of knee arthritis. Mayo Clinic physiatrists have used PRP to treat tendon, ligament and joint disorders for many years to reduce pain and improve function. The effect of PRP on hip arthritis has not been well-studied. Given the high prevalence of hip arthritis and limited nonsurgical treatment options, Mayo researchers believe that this is an important topic to study.