title: 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.
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.
authors.affiliation: Institut de Teràpia Regenerativa Tissular (ITRT), Hospital Quirón Teknon, Carrer de Vilana, 12, 08022 Barcelona, Spain.
authors.forename: Robert
authors.initials: R
authors.lastname: Soler
authors.affiliation: Institut de Teràpia Regenerativa Tissular (ITRT), Hospital Quirón Teknon, Carrer de Vilana, 12, 08022 Barcelona, Spain.
authors.forename: Lluis
authors.initials: L
authors.lastname: Orozco
authors.affiliation: Institut de Teràpia Regenerativa Tissular (ITRT), Hospital Quirón Teknon, Carrer de Vilana, 12, 08022 Barcelona, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Munar
authors.affiliation: Department of Magnetic Resonance Imaging, CETIR Clínica del Pilar, Carrer de Balmes, 271, 08006 Barcelona, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Huguet
authors.affiliation: Divisió de Teràpies Avançades/XCELIA, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005 Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: López
authors.affiliation: Divisió de Teràpies Avançades/XCELIA, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005 Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Vives
authors.affiliation: Divisió de Teràpies Avançades/XCELIA, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005 Barcelona, Spain.
authors.forename: Ruth
authors.initials: R
authors.lastname: Coll
authors.affiliation: Divisió de Teràpies Avançades/XCELIA, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005 Barcelona, Spain.
authors.forename: Margarita
authors.initials: M
authors.lastname: Codinach
authors.affiliation: Divisió de Teràpies Avançades/XCELIA, Banc de Sang i Teixits, Edifici Dr. Frederic Duran i Jordà, Passeig Taulat, 116, 08005 Barcelona, Spain; Chair of Transfusion Medicine and Cellular and Tissue Therapies, Universitat Autònoma de Barcelona, Campus UAB, Cerdanyola del Vallès, 08193 Bellaterra, Spain. Electronic address: joangarcia@bst.cat.
authors.forename: Joan
authors.initials: J
authors.lastname: Garcia-Lopez
mesh_terms: D000328:Adult; D018771:Arthralgia / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D002358:Cartilage, Articular / Q000000981:diagnostic imaging / Q000502:physiology*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D008279:Magnetic Resonance Imaging; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000502:physiology; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000628:therapy*; D011446:Prospective Studies; D011788:Quality of Life; D012038:Regeneration / Q000502:physiology*; D014182:Transplantation, Autologous; D016896:Treatment Outcome
keywords: Articular cartilage; Mesenchymal Stromal Cells; Osteoarthritis; T2 mapping