Background: There are limited treatment options for tissue restoration and the prevention of degenerative changes
in the knee. Stem cells have been a focus of intense preclinical research into tissue regeneration but limited clinical
investigation. In a randomized, double-blind, controlled study, the safety of the intra-articular injection of human mesenchymal
stem cells into the knee, the ability of mesenchymal stem cells to promote meniscus regeneration following
partial meniscectomy, and the effects of mesenchymal stem cells on osteoarthritic changes in the knee were investigated.
Methods: A total of fifty-five patients at seven institutions underwent a partial medial meniscectomy. A single superolateral
knee injection was given within seven to ten days after the meniscectomy. Patients were randomized to one of three
treatment groups: Group A, in which patients received an injection of 50 · 106 allogeneic mesenchymal stem cells;
Group B, 150 · 106 allogeneic mesenchymal stem cells; and the control group, a sodium hyaluronate (hyaluronic acid/
hyaluronan) vehicle control. Patients were followed to evaluate safety, meniscus regeneration, the overall condition of
the knee joint, and clinical outcomes at intervals through two years. Evaluations included sequential magnetic resonance
Results: No ectopic tissue formation or clinically important safety issues were identified. There was significantly increased
meniscal volume (defined a priori as a 15% threshold) determined by quantitativeMRI in 24%of patients in Group A and 6% in
Group B at twelve months post meniscectomy (p = 0.022). No patients in the control group met the 15% threshold for
increased meniscal volume. Patients with osteoarthritic changes who received mesenchymal stem cells experienced a
significant reduction in pain compared with those who received the control, on the basis of visual analog scale assessments.
Conclusions: There was evidence of meniscus regeneration and improvement in knee pain following treatment with
allogeneic human mesenchymal stem cells. These results support the study of human mesenchymal stem cells for the
apparent knee-tissue regeneration and protective effects.s.