Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial

Yves-Marie Pers (1, 2) , Lars Rackwitz (3) , Rosanna Ferreira (4) , Oliver Pullig , Christophe Delfour (5) , Frank Barry (6) , Luc Sensebe (7) , Louis Casteilla (8) , Sandrine Fleury (8) , Philippe Bourin (9) , Danièle Noël (1) , François Canovas (10) , Catherine Cyteval (2) , Gina Lisignoli (11) , Joachim Schrauth (12) , Daniel Haddad (13) , Sophie Domergue (13) , Ulrich Noeth (12) , Christian Jorgensen (1)

1 Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB)
2 CHU - Hôpital Lapeyronie [Montpellier]
3 JMU - Julius-Maximilians-Universität Würzburg
4 Département de Rhumatologie[Montpellier]
5 CHU Montpellier
6 NUI Galway - National University of Ireland [Galway]
7 EFS Alpes-Méditerranée - Établissement Français du Sang Alpes-Méditerranée
8 STROMALab
9 EFS
10 CHRU Montpellier - Centre Hospitalier Régional Universitaire [Montpellier]
11 Istituto Ortopedico Rizzoli Bologna
12 University of Würzburg
13 Hôpital Gui de Chauliac [CHU Montpellier]

Osteoarthritis x Adipose mesenchymal stromal cells x Intra-articular injection x Therapeutic potential x Regenerative medicine x Phase I clinical trial ABSTRACT Osteoarthritis (OA) is the most widespread musculoskeletal disorder in adults. It leads to cartilage damage associated with subchondral bone changes and synovial inflammation, causing pain and disability. The present study aimed at evaluating the safety of a dose-escalation protocol of intra-articular injected adipose-derived stromal cells (ASCs) in patients with knee OA, as well as clinical efficacy as secondary endpoint. A bicentric, uncontrolled, open phase I clinical trial was conducted in France and Germany with regulatory agency approval for ASC expansion procedure in both countries. From April 2012 to December 2013, 18 consecutive patients with symptomatic and severe knee OA were treated with a single intra-articular injection of autologous ASCs. The study design consisted of three consecutive cohorts (six patients each) with dose escalation: low dose (2 3 10 6 cells), medium dose (10 3 10 6), and high dose (50 3 10 6). The primary outcome parameter was safety evaluated by recording adverse events throughout the trial, and secondary parameters were pain and function subscales of the Western Ontario and McMaster Universities Arthritis Index. After 6 months of follow-up, the procedure was found to be safe, and no serious adverse events were reported. Four patients experienced transient knee joint pain and swelling after local injection. Interestingly, patients treated with low-dose ASCs experienced significant improvements in pain levels and function compared with baseline. Our data suggest that the intraarticular injection of ASCs is a safe therapeutic alternative to treat severe knee OA patients. A placebo-controlled double-blind phase IIb study is being initiated to assess clinical and structural efficacy.

Mots clés: Osteoarthritis; Phase I clinical trial; Regenerative medicine; Therapeutic potential.; Adipose mesenchymal stromal cells; Intra-articular injection

Domaines: Sciences du Vivant [q-bio]

Yves-Marie Pers, Lars Rackwitz, Rosanna Ferreira, Oliver Pullig, Christophe Delfour, et al.. Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. Stem Cells Translational Medicine, 2016, 5 (7), pp.847 - 856. ⟨10.5966/sctm.2015-0245⟩. ⟨hal-01834263⟩