Abstract
Adipose derived mesenchymal stromal cells (ASC) are adult stem cells exhibiting functional properties that have open the way for cell-based clinical therapies. Primarily, their capacity of multilineage differentiation has been explored in a number of strategies for skeletal tissue regeneration. More recently, MSCs have been reported to exhibit immunosuppressive as well as healing capacities, to improve angiogenesis and prevent apoptosis or fibrosis through the secretion of paracrine mediators. Among the degenerative diseases associated with aging, osteoarthritis is the most common pathology and affects 16% of the female population over 65 years. Up to now, no therapeutic option exists to obtain a sustainable improvement of joint function beside knee arthroplasty. This prompted us to propose adipose derived stem cells as a possible cell therapy. We performed pre-clinical models of osteoarthritis and showed that a local injection of ASC showed a reduction of synovitis, reduction of osteophytes, joint stabilization, reducing the score of cartilage lesions. This work was completed by toxicology data showing the excellent tolerance of the local injection of ADSC and biodistribution showing the persistence of cells after 6 months in murine models. The aim of the ADIPOA trial is to demonstrate the efficacy of adipose derived stem cells therapy in knee osteoarthritis (OA) in a phase 2/3 controlled multicenter study controlled against standard of care. Safety and feasibility as well as dose response was previously assessed in the ADIPOA FP7 project. The bi-centric phase I clinical trial in Montpellier (France) and Würzburg (Germany) included 18 patients with moderate to severe knee OA, each patient received a single injection of autologous ADSC, in a open scale up dose trial, starting form 2 10 6 cells to 50 106 cells. The 107 dose appears to be well tolerated and showed preliminary response in terms of decreasing local inflammation. This first study confirmed the feasibility and safety of local injection of ADSC in knee OA and suggested the most effective dose (107 autologous ADSC). This work constituted a significant step forward treating this disease with ADSC to demonstrate safety of the procedure.
we conduct a prospective multicenter randomized Phase 2/3 study with 86 patients with moderate to severe knee OA to demonstrate superiority of stem cell-based therapy compared to standard of care (SOC) in terms in reduction in clinical symptoms (WOMAC score) and structural benefit (assessed by T1rhoMRI that allow quantification of cartilage proteoglycan content). This project will offer EU a unique leadership in OA with strong positions in EU and US due to patents and quality of the methodology to demonstrate efficiency of ADSC. ADIPOA brings together a unique combination of expertises and leaders in clinical rheumatology, MRI specialists, Stem cell Institutes, national GMP grade adipose derived stem cell production platform (ECELLFRANCE) and SME specialized in cell therapy trials in the EU. The production of the cells will be granted to EFS through ECELLFRANCE national platform, which have the GMP facility and will work as a contracting manufacturing organization. The expertise, leadership and critical mass achieved by this Consortium should enable breakthroughs in ASC engineering directly amenable for clinical applications in OA.
