Human autologous mesenchymal stromal cells for the treatment of mid- to late-stage knee osteoarthritis—preliminary results from a first-in-North America phase I/II study

      We have initiated a Phase I/II clinical trial using autologous bone marrow- derived mesenchymal stromal cells (BM-MSCs) to treat moderate to severe knee osteoarthritis (OA), the first such study in Canada. This is a non-randomized, open-label, dose-escalation trial with 12 patients between aged 40 to 65 with Kellgren-Lawrence III or IV OA of the knee. Patients received autologous BM-MSCs at 1 million, 10 million or 50 million cell doses under ultrasound guidance in a single intra-articular injection in the affected knee. MSCs were qualified for safety, identity and some potency markers. All patients are prospectively evaluated at baseline and at multiple time points (2 days, 1, 2 and 6 weeks, 3, 6, and 12 months and yearly thereafter for 4 years). The primary outcome is safety as determined by the occurrence of local and systemic adverse events and/or serious adverse events. Secondary outcomes include: (1) Knee Injury and Osteoarthritis Outcome Score (KOOS); (2) Marx Activity Scale; (3) health-related quality of life as determined by the Short-Form 36; (4) Whole Organ MRI Score (WORMS) and T2 maps post-gadolinium scored for synovitis and inflammatory changes; (5) serum and urine biomarkers of cartilage metabolism, and (6) synovial fluid markers of inflammation and infiltrating immune cells. To date, twelve patients have been enrolled with a mean age of 56 years (range 46–65), 7/12 male. We conclude that BM-MSCs are safe when injected into the knee at all doses examined. In the 1 million dose group, 2/3 patients achieved Minimal Clinically Important Difference (MCID) of 10 in KOOS pain and QOL scores at 3 months and maintained for 6–12 months; 2/3 patients achieved MCID of 10 in pain and QOL in the 10 million dose group at 3 months and retained for 6 months; 2/3 in the 50 million dose group achieved MCID of 10 for pain and QOL at 3 months, based on currently available data. Six-month and 12-month MRI and X-ray data are available for 7/12 and 4/12 patients respectively, with complete data available in December 2017. Preliminary analysis of MR images did not reveal changes in cartilage volume, but did show MSC-mediated changes in synovitis. With a dose titration at the lower end of the spectrum, and an emphasis on measuring inflammatory biomarkers, this trial should result in some novel efficacy observations, in addition to safety parameters.
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