title: Adult human mesenchymal stem cells delivered via intra-articular injection to the knee following partial medial meniscectomy: a randomized, double-blind, controlled study.
abstract: 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.
authors.affiliation: University of Southern California Orthopaedic Surgery Associates, Keck School of Medicine, 1520 San Pablo Street, Suite 2000, Los Angeles, CA 90033. E-mail address: vangsness@usc.edu.
authors.forename: C Thomas
authors.initials: CT
authors.lastname: Vangsness
authors.affiliation: OrthoIndy, 5255 East Stop 11 Road, Suite 300, Indianapolis, IN 46237.
authors.forename: Jack
authors.initials: J
authors.lastname: Farr
authors.affiliation: TRIA Orthopaedic Center, 8100 Northland Drive, Bloomington, MN 55431.
authors.forename: Joel
authors.initials: J
authors.lastname: Boyd
authors.affiliation: Triangle Orthopaedic Associates, PA, 120 William Penn Plaza, Durham, NC 27704.
authors.forename: David T
authors.initials: DT
authors.lastname: Dellaero
authors.affiliation: Osiris Therapeutics, Inc., 7015 Albert Einstein Drive, Columbia, MD 21046.
authors.forename: C Randal
authors.initials: CR
authors.lastname: Mills
authors.affiliation: Osiris Therapeutics, Inc., 7015 Albert Einstein Drive, Columbia, MD 21046.
authors.forename: Michelle
authors.initials: M
authors.lastname: LeRoux-Williams
mesh_terms: D000328:Adult; D000368:Aged; D001182:Arthroscopy / Q000379:methods; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage; D007270:Injections, Intra-Articular; D007592:Joint Diseases / Q000175:diagnosis / Q000601:surgery*; D007719:Knee Joint / Q000503:physiopathology / Q000601:surgery*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008592:Menisci, Tibial / Q000473:pathology / Q000601:surgery*; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D008875:Middle Aged; D010147:Pain Measurement; D061214:Patient Safety; D020127:Recovery of Function; D012016:Reference Values; D018570:Risk Assessment; D012720:Severity of Illness Index; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D006820:Hyaluronic Acid