Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study.

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 imaging (MRI). 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 quantitative MRI 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.

Allograft transplantation in the knee: tissue regulation, procurement, processing, and sterilization.

Use of musculoskeletal allografts has become increasingly popular, with widespread use among knee surgeons. The advantages and disadvantages of their use have been documented. In the knee, allografts are used for ligament reconstruction, meniscal transplantation, and articular surface reconstruction. The purpose of this review is to present issues surrounding the allograft industry, including regulation of tissues and tissue banks and procurement, processing, sterilization, and storage of allograft tissue. Tissue bank regulation is ultimately under the jurisdiction and authority of the Food and Drug Administration; some individual states regulate tissue banks. The American Association of Tissue Banks is a scientific organization that encourages education, research, and voluntary accreditation of tissue banks. It promotes safety and standards for retrieval, processing, storage, and distribution of transplantable human tissue. Allograft tissues are generally harvested and processed aseptically, which may not prevent contamination. Tissue sterilization is difficult and controversial. Tissue banks historically have used one of two methods of sterilization, ethylene oxide or gamma radiation. Both methods have risks and benefits. Newer methods of sterilization are being developed. Allograft tissue that is not transplanted fresh can be freeze-dried or deep frozen for storage. Ultimately, allograft transplantation in the knee facilitates knee form and function and enhances the patient's quality of life. Orthopaedic surgeons who use allograft tissue must understand the tissue banking process to provide safe and effective tissues to their patients.