Oct. 24, 2017
Osteoarthritis (OA) is the most common joint disease worldwide. Within the United States nearly 30 million people are affected, and the cost of treating this disease is well over $100 billion annually.
The knee is the joint most commonly affected by OA. Currently, most available nonsurgical treatments for OA of the knee are palliative, controlling symptoms rather than curing the disease. These treatments include oral nonsteroidal anti-inflammatory medications, viscosupplementation and intra-articular corticosteroid therapies.
Although effective at relieving acute pain symptoms, currently available nonsurgical treatments are associated with significant potential for adverse side effects, and they do not slow or reverse disease progression. The only complete cure is a total knee arthroplasty. To address this challenge, researchers across the globe are searching for nonsurgical interventions that will alter the course of this disease or prevent it.
Derived from the stromal vascular fraction of adipose tissue, adipose-derived mesenchymal stem cells (AMSCs) are immature mesenchymal cells with stem cell-like properties. AMSCs have received increasing attention as a possible therapeutic agent for OA of the knee. Stem cells exist throughout the body, but they are particularly prevalent in bone marrow and in fat. Stem cells harvested from fat also grow quickly and are quite resilient when grown in the laboratory.
In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, Mayo Clinic researchers conducted animal studies using rabbits that demonstrated a favorable safety profile for AMSCs within the joint space. Researchers delivered culture-expanded human AMSCs, grown in human platelet-lysate, via intra-articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy.
Published in Stem Cells Translational Medicine in 2017, the animal studies yielded promising results. Mayo researchers noted that the post-treatment assessment of the animals' general health, function and behavior, and the assessment of joint tissues, analyzed by X-ray, magnetic resonance imaging and histopathology, demonstrated that intra-articular AMSC therapy was well-tolerated. Researchers did not observe adverse systemic reactions or evidence of damage to intra-articular joint tissues. These results paved the way for the phase I clinical trial evaluating the clinical utility of AMSCs to treat osteoarthritis that is now underway.
The primary goal of the current phase I clinical trial is to study the safety of using AMSCs in the treatment of knee osteoarthritis. This study is the first of its kind to be conducted in the United States and the first in the world to test both single and multiple injections of AMSCs in human subjects.
The clinical trial involves 20 healthy participants with knee OA. The stem cells are extracted from the participant's abdominal fat, grown in a laboratory until they reach sufficient numbers and then injected into the knee. Participants are divided into four groups, each of which receives a different dosing regimen. Anywhere from 50 to 300 million stem cells are injected into the knee over a one- to three-month period. Mayo researchers will follow patients from one to two years after treatment.
"We are hopeful that the clinical trial that we are currently conducting will yield results that will bring us closer to finding a nonsurgical intervention for knee osteoarthritis," says the study's principal investigator Jay Smith, M.D., vice chair of Physical Medicine and Rehabilitation at Mayo Clinic's campus in Rochester, Minnesota. "If the results of this study are promising, we would hope to offer this treatment to patients as soon as possible."
Study inclusion criteria
Mayo investigators are recruiting otherwise healthy individuals who meet the following inclusion criteria:
- Male or female age 40 to 70 years
- Chronic (> 3 months), unilaterally symptomatic, primary femorotibial knee osteoarthritis
- Radiographic medial and/or lateral femorotibial knee OA at least Kellgren-Lawrence grade 2
- Previous six-week or longer trial of one of the following conservative treatments
- Activity modification
- Weight loss
- Physical therapy
- Anti-inflammatory medications or injection therapy (e.g., cortisone, hyaluronic acid/viscosupplement)
- Ability to routinely walk without assistance (e.g., cane, walker)
- Clinically stable target knee
- No surgery planned in the target knee for at least 12 months following the last injection
- Completion of general physical evaluation with primary care provider within 12 months of enrollment
Females of childbearing potential must have a negative pregnancy test prior to participating and agree to use adequate contraception until one year after completing treatment. A complete list of eligibility criteria for this study is available on Mayo Clinic's clinical trials website.
For more information
Riester SM, et al. Safety studies for use of adipose tissue-derived mesenchymal stromal/stem cells in a rabbit model for osteoarthritis to support a phase I clinical trial. Stem Cells Translational Medicine. 2017;6:910.
Mayo Clinic. A study of the safety and usability of culture expanded STEM cells derived from the patient's own fat tissue for treatment of knee osteoarthritis. MayoClinic.org