The results of a clinical trial using bone marrow-derived mesenchymal stromal cells (MSCs) to treat late-stage knee osteoarthritis were published recently, and they came back positive. The trial included both phase 1 and 2 and was designed to determine the safety and efficacy of MSC stem cell therapy.
A battery of tests
During the trial, patients were given a single injection of 1, 10, or 50 million MSCs directly into the knee. The trial used a number of tests associated with knee osteoarthritis, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), a common set of standardized questionnaires used by healthcare professionals to evaluate the condition of patients with osteoarthritis of the knee. The WOMAC includes questions relating to pain, stiffness, and the physical functioning of the joints.
The trial also used the Knee Injury and Osteoarthritis Outcome Score (KOOS), which was developed as an extension of the WOMAC as a means of evaluating short-term and long-term symptoms and function.
Patient-reported outcome measures (PROMs), which measure the outcomes of procedures from the patient’s perspective, were also part of the trial. Patients complete questionnaires both before the procedure and 3-6 months after it. This helps to assess the longer-term outcome for patients and informs future therapeutic direction.
The study also used various biomarkers typically associated with the condition, including MRI scans for changes to cartilage, collagen levels, synovitis biomarkers, inflammatory biomarkers, and cartilage turnover rate. All of these markers were taken over a 12-month period.
Positive results from a single injection
The majority of these markers showed some level of improvement, and those improvements scaled with the amount of MSCs injected, with the larger doses giving better results. The researchers observed that the beneficial effects were associated with a reduction of inflammation and pain as well as a slowing down of osteoarthritis progression. This is consistent with other studies which show that MSCs have an anti-inflammatory effect on tissues, and the data supports the hypothesis that MSC stem cells facilitate the healing of damaged joints through the various factors that they secrete
There was no evidence of cartilage regeneration in these patients; the researchers believe that this was because the patients in this study had end-stage osteoarthritis and were aged between 40 and 65. In other studies, researchers have reported seeing cartilage regeneration, though this may have been because the patients were either younger or at less advanced stages of the disease. On the plus side, the therapy did appear to protect the existing cartilage for at least a 12-month period following the therapy.
The therapy was well tolerated, with only four of the patients experiencing an adverse effect, which was pain and swelling at the site of injection. This minor side effect subsided by itself, did not require any intervention, and is a typical reaction seen in various stem cell trials.
Patients with late‐stage Kellgren‐Lawrence knee osteoarthritis received a single intra‐articular injection of 1, 10, or 50 million bone marrow mesenchymal stromal cells (BM‐MSCs) in a phase I/IIa trial to assess safety and efficacy using a broad toolset of analytical methods. Besides safety, outcomes included patient‐reported outcome measures (PROMs): Knee Injury and Osteoarthritis Outcome Score (KOOS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC); contrast‐enhanced magnetic resonance imaging (MRI) for cartilage morphology (Whole Organ MRI Scores [WORMS]), collagen content (T2 scores), and synovitis; and inflammation and cartilage turnover biomarkers, all over 12 months. BM‐MSCs were characterized by a panel of anti‐inflammatory markers to predict clinical efficacy. There were no serious adverse events, although four patients had minor, transient adverse events. There were significant overall improvements in KOOS pain, symptoms, quality of life, and WOMAC stiffness relative to baseline; the 50 million dose achieved clinically relevant improvements across most PROMs. WORMS and T2 scores did not change relative to baseline. However, cartilage catabolic biomarkers and MRI synovitis were significantly lower at higher doses. Pro‐inflammatory monocytes/macrophages and interleukin 12 levels decreased in the synovial fluid after MSC injection. The panel of BM‐MSC anti‐inflammatory markers was strongly predictive of PROMs over 12 months. Autologous BM‐MSCs are safe and result in significant improvements in PROMs at 12 months. Our analytical tools provide important insights into BM‐MSC dosing and BM‐MSC reduction of synovial inflammation and cartilage degradation and provide a highly predictive donor selection criterion that will be critical in translating MSC therapy for osteoarthritis.
This is a positive result for stem cell therapy, and it is great to see a successful clinical trial demonstrating the benefits of MSC therapy. In the current climate of FDA crackdowns on rogue clinics selling dubious and untested stem cell therapies, it is good to see things being done properly, passing through clinical trials, and delivering positive results for osteoarthritis patients. Hopefully, these results will encourage health regulators to move forwards in approving this therapy in the United States for the treatment of osteoarthritis.