title: The Effect of Cell Dose on the Early Magnetic Resonance Morphological Outcomes of Autologous Cell Implantation for Articular Cartilage Defects in the Knee: A Randomized Clinical Trial.
abstract: Although autologous chondrocyte implantation (ACI) has been established as a standard treatment for large full-thickness cartilage defects, the effect of different doses of autologous chondrocyte products on structural outcomes has never been examined.
  
  
  
  In ACI, the dose level may have an influence on medium-term magnetic resonance morphological findings after treatment.
  
  
  
  Randomized controlled trial; Level of evidence, 1.
  
  
  
  A total of 75 patients who underwent ACI using a pure, autologous, third-generation matrix-associated ACI product were divided into 3 groups representing different doses: 3 to 7 spheroids/cm(2), 10 to 30 spheroids/cm(2), and 40 to 70 spheroids/cm(2). Magnetic resonance imaging was performed at 1.5, 3, 6, and 12 months after ACI and was evaluated by the magnetic resonance observation of cartilage repair tissue (MOCART) score and the Knee injury and Osteoarthritis Outcome Score (KOOS).
  
  
  
  MOCART scores showed improvements after 3 months, with slight dose dependence, and further improvement after 12 months, although without significant dose dependence. The mean MOCART scores after 3 months (0 = worst, 100 = best) were 59.8, 64.5, and 64.7 for the low-, medium-, and high-dose groups, respectively, and 62.9 for all patients; at 12 months, these were 74.1, 74.5, and 68.8 for the respective dose groups and 72.4 for all patients. Several MOCART items (surface of repair tissue, structure of repair tissue, signal intensity of repair tissue, subchondral bone, and synovitis) showed a more rapid response with the medium and high doses than with the low dose, suggesting a potential dose relationship. No significant correlation between the MOCART (overall and subscores) with clinical outcomes as assessed by the overall KOOS was detected at 3- and 12-month assessments.
  
  
  
  This study reveals a trend toward earlier recovery after treatment with higher spheroid doses in terms of better defect filling for full-thickness cartilage defects of the knee, while outcomes after 12 months were similar in all dose groups. However, a correlation with clinical outcomes or the failure rate at 1 year after ACI was not found. A longer follow-up will be required for more definite conclusions on the clinical relevance of ACI cell density to be drawn.
  
  
  
  NCT01225575 (ClinicalTrials.gov identifier); 2009-016816-20 (EudraCT number).
authors.affiliation: Department of Orthopedic Surgery and Traumatology, Freiburg University Hospital, Freiburg, Germany philipp.niemeyer@uniklinik-freiburg.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Niemeyer
authors.affiliation: Joint and Spine Centre Berlin, Berlin, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Laute
authors.affiliation: Clinic for Traumatology and Orthopedic Surgery, DRK Hospital Berlin Westend, Berlin, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: John
authors.affiliation: Department of Orthopedic Surgery, Medical University Annastift Hannover, Hannover, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Becher
authors.affiliation: Department of Orthopedic Surgery, University of Rostock, Rostock, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Diehl
authors.affiliation: Traumatology and Reconstructive Surgery, DRK Hospital Luckenwalde, Luckenwalde, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kolombe
authors.affiliation: Department of Traumatology and Arthroscopic Surgery, Lubinus Clinicum Kiel, Kiel, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: Fay
authors.affiliation: Center for Hip, Knee and Foot Surgery, ATOS Clinic Heidelberg, Heidelberg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Siebold
authors.affiliation: Department of Orthopedic Surgery and Traumatology, Mannheim University Hospital, Mannheim, Germany.
authors.forename: Milan
authors.initials: M
authors.lastname: Niks
authors.affiliation: Sporthopaedicum Straubing, Straubing, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Fickert
authors.affiliation: Department of Orthopedic Surgery and Traumatology, St Vinzenz-Hospital Dinslaken, Dinslaken, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Zinser
mesh_terms: D000293:Adolescent; D000328:Adult; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000601:surgery*; D019902:Chondrocytes / Q000637:transplantation*; D005260:Female; D006801:Humans; D007718:Knee Injuries / Q000000981:diagnostic imaging / Q000601:surgery*; D007719:Knee Joint / Q000000981:diagnostic imaging / Q000601:surgery*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019637:Orthopedic Procedures; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000601:surgery*; D011446:Prospective Studies; D014182:Transplantation, Autologous / Q000379:methods; D055815:Young Adult
keywords: KOOS; MOCART; autologous chondrocyte implantation; cartilage lesion; knee surgery; randomized clinical trial