A single injection of mesenchymal stem cells (MSCs) into the meniscus after knee surgery is safe, relieves osteoarthritis (OA) pain, and may facilitate regeneration, according to results of a small study published in the January 15 issue of the Journal of Bone and Joint Surgery. However, at least one expert questions the clinical utility of the approach.
At least a million people undergo knee arthroscopy in the United States annually, but the failure rate is 20% to 24%. Partial lateral meniscectomy increases the risk of developing OA 10- to 20-fold in the months and years after surgery. Restorative procedures are limited and include an allograft or scaffold implant (not available in the United States).
MSCs are among the best-studied stem cells, and in animal models, they stimulate meniscus regeneration. The cells divide to give rise to cells that differentiate as connective tissues. MSCs also have anti-inflammatory and immunomodulatory effects.
Therefore, C. Thomas Vangsness Jr, MD, from the Keck School of Medicine of the University of Southern California in Los Angeles, and colleagues conducted a phase 1/2 randomized, double-blind controlled study on the use of MSCs to alleviate pain and regenerate cartilage after meniscectomy.
Fifty-five patients aged 18 to 60 years who underwent partial medial meniscectomy received a single injection into the knee 7 to 10 days after surgery. Group A (n = 18) received 50 million MSCs, group B (n = 18) received 150 million cells, and group C (n = 19), the control, received sodium hyaluronate, the matrix in which the MSCs were suspended in the other groups.
The researchers used magnetic resonance imaging to evaluate safety, meniscus regeneration, and overall condition of the knee joint at 6 weeks, 6 months, 1 year, and 2 years after surgery. Participants reported pain and knee function using a visual analog scale and the Lysholm knee scale.
Osiris Therapeutics funded the study and provided the MSCs, which came from the bone marrow of healthy volunteers aged 18 to 30 years.
The treatment appeared to be safe. No ectopic tissue formed. Meniscal volume increased more than 15% in 4 (24%) of 17 patients in group A (low dose) and in 1 (6%) of 18 patients in group B (high dose) at 1 year (P = .022). Volume increase was not statistically significant at 2 years, persisting in only 3 patients, all from group A. Meniscal volume did not exceed threshold in any control patients.
Patients with OA who were given stem cells reported greater pain relief than control patients who have OA. At the study's start, OA affected 7 patients in the control group, 11 patients in group A, and 12 patients in group B. At baseline, knee pain was similar across the groups.
On the 100-mm visual analog scale for pain, "[t]he average relative improvement was 18.8 mm at six weeks, increasing to 27.3 mm at two years, for Group A. A comparable increase was seen for Group B, which had a relative difference of 14.6 mm at six weeks and 24.1 mm at two years," the researchers write. The researchers write that they observed "strong trends or significant" differences at 2 years for group A (P = .05) compared with the control group, and at 1 (P = .08) and 2 (P = .04) years for group B.
The study provides evidence of safety, improvement in knee pain, and meniscus regeneration, the researchers conclude.
Study limitations include inconsistency of MRI scan interpretation from different institutions and a difference in the percentage of patients with OA across groups. Further investigation is necessary to determine whether or not a higher dose of MSCs or additional injections of any dosage are beneficial.
In an accompanying commentary and perspective, Henry B. Ellis, MD, from Texas Scottish Rite Hospital for Children in Dallas, points out that the small group sizes may be problematic because the members of the control group weighed significantly less and because fewer of them had OA than members of the groups given MSCs.
Dr. Ellis also states that the approach may not help many people. Of the 35 patients who received MSCs, only 5 (14%) had increased meniscal volume at 1 year and only 3 (9%) had increased volume at 2 years. "Although the authors demonstrated a statistically significant difference, does this really demonstrate clinical relevance?" Dr. Ellis writes. He concludes that the evidence supports pain relief from MSCs but not yet sufficient regeneration in enough patients for clinical utility.
Osiris Therapeutics funded the study. The authors and commentator have disclosed no relevant financial relationships.
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Cite this: Stem Cells Safe, Reduce Arthritis Pain After Knee Surgery - Medscape - Jan 21, 2014.