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.
In this open-label phase 1 trial we included 18 patients with severe osteoarthritis of the knee in failure of conventional therapies (62.5% were KL IV) at two sites, Montpellier and Wurzburg. Mean age was 61 years, with a 10 years history of knee OA. The patient received a single injection of autologous ASC 15 days after lipoaspiration (2.106, 107 or 5.107) through intra-articular injection. The primary outcome measure of effectiveness was patient-reported WOMAC pain subscores by VAS in the affected knee at week 12. Secondary outcome measures included Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT OARSI) responses. We observed a decrease of the VAS Pain (73±11 mm day 0 to 32±23 month 3), and of WOMAC (50±18 to 25±7 month 3). This study confirms the feasibility and safety of local injection of autologous cells from adipose tissue and suggested that the most effective dose was 107 autologous cells.
The ADIPOA research teams performed successfully the phase 1 clinical trial is in France and Germany. A phase 2B controlled trial is scheduled to confirm the clinical benefit of this strategy.
Disclosure of Interest None declared