Oct. 04, 2024
Low back pain (LBP) affects approximately 84% of the adult population and is the leading cause of disability worldwide. Although LBP has multiple causes and risk factors, from 15% to 40% of people have pain stemming from lumbar facet joint arthropathy (LFJA).
Comprised of cartilage, articular capsule and synovium, lumbar facet joints facilitate flexibility and movement of the spinal column. LFJA is a broad term encompassing age-related, degenerative and proliferative changes that can affect these synovial joints, including the narrowing of joint spaces, subarticular bone erosions, subchondral edema, osteophyte formation and hypertrophy of the articular processes. Risk factors for LFJA can include history of degenerative disk disease, trauma, poor body mechanics, obesity and genetic traits.
Conservative treatments for LFJA include oral analgesics and physical therapy. When conservative treatments are not beneficial, corticosteroid injections, medial branch nerve block or radiofrequency rhizotomy may be recommended.
Unfortunately, most of the available treatment options focus on symptomatic relief rather than addressing the underlying degenerative process of LFJA and fail to provide long-term pain relief. To address this problem, Mayo Clinic researchers are conducting a phase 1 clinical trial evaluating the safety and preliminary efficacy of allogenic, culture-expanded bone marrow-derived mesenchymal stem cells (BM-MSCs) in patients with painful LFJA.
Mayo Clinic physiatrist and pain specialist Wenchun Qu, M.D., Ph.D., notes that this clinical trial is part of multiple research efforts that he and colleagues are conducting to evaluate regenerative medicine therapies for the treatment ofback, neck and knee pain caused by degenerative arthritis. Dr. Qu is the Jorge and Leslie Bacardi Associate Director of the Center for Regenerative Biotherapeutics at Mayo Clinic in Florida.
"MSCs have attracted significant interest for the treatment of symptomatic synovial joint degeneration due to their anti-inflammatory and immunomodulating effects and low immunogenicity," explains Dr. Qu. "However, the role of BM-MSCs in treating patients with LFJA has not yet been thoroughly studied."
In a case report published in PAIN Reports in 2024, Dr. Qu and Mayo Clinic colleagues describe their study methods and initial reports from the first treated patient in a phase 1 clinical trial.
Methods
The clinical trial is designed to evaluate the safety and feasibility of intra-articular administration of allogenic BM-MSCs for painful FLJA.
The study participant was a 61-year-old female who experienced low back pain for more than three years. The participant described her pain as 8 out of 10 on the Visual Analogue Scale (VAS) that was exacerbated by bending the lumbar spine backward and engaging in vigorous physical activities. The participant did not recall a fall or traumatic event that precipitated the pain.
Previous back pain care, including facet joint corticosteroid injections, several facet medial branch radiofrequency ablations, physical therapy exercises and transcutaneous electrical nerve stimulation (TENS), did not provide long-term benefits. Physical examination was positive for bilateral lower lumbar facet loading maneuvers and lower lumbar paraspinal tenderness. Her lumbar MRI indicated suspected bilateral facet synovitis (LFJA) at L3-L4, while severe LFJA was noted at L4-L5, with severe right-sided facet synovitis.
The treatment consisted of a single injection of two joints, each containing 10 million BM-MSCs in a 1 mL syringe. The patient was evaluated before treatment, at treatment and during two years of standardized follow-up. Evaluation included a full spine-focused neuromusculoskeletal physical examination and clinical assessments of low back pain and function and blood sample analysis. Assessment tools included the Patient-Reported Outcomes Measurement Information System — Computer Adaptive Testing (PROMIS CAT), lumbar spine radiographs, work functional status and narcotic pain medication use questionnaires, and MRI Fenton-Czervionke scoring.
Results
The researchers report that the patient tolerated the procedure well and did not experience any significant treatment-related adverse events during the study period. The patient's pain symptoms, spine function and work functional status showed improvement at multiple follow-up visits. At the one-year follow-up, MRI evaluation revealed a decrease in the grade of facet synovitis. Additionally, the patient reported mental and social health improvements.
"Our case report suggests that administering intra-articular allogeneic BM-MSCs has a favorable feasibility and safety profile. And this treatment may have the potential to offer meaningful therapeutic benefits for pain management, functional activities and imaging changes. While this case shows safety and pain relief for cell therapy, we are looking forward to having data from the entire phase 1 study to inform us with more certainty."
Conclusions
"Our case report suggests that administering intra-articular allogeneic BM-MSCs has a favorable feasibility and safety profile. And this treatment may have the potential to offer meaningful therapeutic benefits for pain management, functional activities and imaging changes," says Dr. Qu. "While this case shows safety and pain relief for cell therapy, we are looking forward to having data from the entire phase 1 study to inform us with more certainty. We will need further randomized trials to examine efficacy and safety. This study contributes to the literature and serves as a foundation. I truly appreciate our team that does a fantastic job."
For more information
Yan D, et al. CellKine clinical trial: first report from a phase 1 trial of allogeneic bone marrow-derived mesenchymal stem cells in subjects with painful lumbar facet joint arthropathy. PAIN Reports. 2024;9:e1181.
Clinical Trials: Study evaluating the side effects of bone marrow-derived stem cells when injected into the facet joints for the treatment of painful arthropathies. Mayo Clinic.
Refer a patient to Mayo Clinic.