Final results of a phase I-II trial using ex vivo expanded autologous Mesenchymal Stromal Cells for the treatment of osteoarthritis of the knee confirming safety and suggesting cartilage regeneration

Knee. 2016 Aug;23(4):647-54. doi: 10.1016/j.knee.2015.08.013. Epub 2016 Jan 11.

Abstract

Background: Cellular therapies have shown encouraging results in the treatment of chronic osteoarthritis (OA). Herein, we present the final results of a phase I-II clinical trial assessing the feasibility, safety and efficacy of ex vivo expanded autologous bone marrow Mesenchymal Stromal Cells (MSC, XCEL-M-ALPHA), infused intra-articularly, in patients with knee OA.

Methods: Fifteen patients (median age=52years) with grade II(9) or III(6) gonarthrosis (Kellgren & Lawrence classification) and chronic pain were treated with an intra-articular infusion of 40.9×10(6)±0.4×10(6) MSCin a phase I-II prospective, open-label, single-dose, single-arm clinical trial. Endpoints were safety and tolerability. Efficacy was measured by the Visual Analogue Scale for pain, algofunctional Health Assessment Questionnaire, Quality of Life (QoL) SF-36 questionnaire, Lequesne functional index and WOMAC score. Cartilage integrity was assessed by Magnetic Resonance Imaging and quantitative T2-mapping at 0, 6 and 12months.

Results: The cell-based product was well tolerated with few reported Adverse Events (mild arthralgia and low back pain). There was a relevant decrease in the intensity of pain since day 8 after the infusion, that was maintained after 12months. The SF-36 QoL test showed improvement of parameters including bodily pain, role physical and physical functioning at month 12. The health assessment questionnaire revealed a significant decrease of incapacity. Moreover, T2 mapping showed signs of cartilage regeneration in all patients at 12months post-treatment.

Conclusions: Single intra-articular infusion of XCEL-M-ALPHA is a safe and well-tolerated cell-based product, associated with a long-lasting amelioration of pain, improvement of QoL (up to four years), and signs of cartilage repair.

Keywords: Articular cartilage; Mesenchymal Stromal Cells; Osteoarthritis; T2 mapping.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Arthralgia / diagnostic imaging
  • Arthralgia / physiopathology
  • Arthralgia / therapy*
  • Cartilage, Articular / diagnostic imaging
  • Cartilage, Articular / physiology*
  • Feasibility Studies
  • Female
  • Humans
  • Injections, Intra-Articular
  • Magnetic Resonance Imaging
  • Male
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / physiology
  • Middle Aged
  • Osteoarthritis, Knee / diagnostic imaging
  • Osteoarthritis, Knee / physiopathology
  • Osteoarthritis, Knee / therapy*
  • Prospective Studies
  • Quality of Life
  • Regeneration / physiology*
  • Transplantation, Autologous
  • Treatment Outcome