A Multicenter, Single-Blind, Phase IIa Clinical Trial to Evaluate the Efficacy and Safety of a Cell-Mediated Gene Therapy in Degenerative Knee Arthritis Patients

Hum Gene Ther Clin Dev. 2015 Jun;26(2):125-30. doi: 10.1089/humc.2014.145. Epub 2015 Apr 17.


Osteoarthritis leads to articular cartilage wear, and newer therapies are aimed at slowing this degeneration. Growth factors and cytokines influence cartilage formation, and researchers are studying their use on cartilage regeneration in osteoarthritis. One method uses genetically engineered cells to deliver growth factors to damaged cartilage. This technique utilizes transforming growth factor-β proteins in modified chondrocytes to stimulate cartilage growth via an intra-articular injection. We evaluated the efficacy and outcomes of this injection on patients who had International Cartilage Repair Society grade 4 knee osteoarthritis. We evaluated 27 patients (6 men, 21 women) who had late-stage knee osteoarthritis. Patients were randomized to receive genetically engineered chondrocytes doses of 6×10(6) cells (group 1) or 1.8×10(7) cells (group 2) at a 1:1 ratio. Primary endpoints were subjective and functional evaluations, assessed by the International Knee Documentation Committee (IKDC) score. Secondary endpoints were pain severity and physical function, using the Western Ontario and McMaster osteoarthritis (WOMAC) index and the 100 mm visual analog scale (VAS). Patients were followed at 2, 4, 12, and 24 weeks postinjection. Both groups had significant improvements in outcomes. Scores improved at 12 and 24 weeks from baseline in IKDC (+10 and +14 points in group 1; +11 and +13 points in group 2), WOMAC (-12 and -13 points in group 1; -10 and -12 points in group 2), and VAS (-19 and -24 points in group 1; -20 and -20 in group 2) scores. Additionally, there were no serious adverse events, and no significant difference in adverse event incidence between the groups. Both groups expressed a mean improvement in pain, function, and physical ability following treatment injection. This modality appears to be a promising treatment for cartilage degeneration. However, further larger, multicenter, randomized studies are needed to truly evaluate the efficacy of this novel approach.

Trial registration: ClinicalTrials.gov NCT02341378.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Chondrocytes / transplantation*
  • Female
  • Genetic Therapy*
  • Humans
  • Knee Joint / pathology
  • Knee Joint / physiopathology
  • Male
  • Middle Aged
  • Osteoarthritis, Knee / pathology
  • Osteoarthritis, Knee / physiopathology
  • Osteoarthritis, Knee / therapy*
  • Single-Blind Method
  • Transforming Growth Factor beta1 / genetics*


  • Transforming Growth Factor beta1

Associated data

  • ClinicalTrials.gov/NCT02341378