Journal Article

Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II)

Bondía, José M., Mora, Gonzalo, Villarón, Eva M., del Cañizo, María Consuelo, Nuñez-Córdoba, Jorge M., Valentí-Azcárate, Andrés, Aquerreta, Jesús Dámaso, Ornilla, Enrique, Sánchez-Echenique, Carmen, Andreu, Enrique J., Sánchez-Guijo, Fermín, Prósper, Felipe, Blanco, Juan F., Valentí-Nin, Juan Ramón, Granero-Moltó, Froilán, Lamo-Espinosa, José M.

2016

Overview

Background Mesenchymal stromal cells are a promising option to treat knee osteoarthritis. Their safety and usefulness must be confirmed and the optimal dose established. We tested increasing doses of bone marrow mesenchymal stromal cells (BM-MSCs) in combination with hyaluronic acid in a randomized clinical trial. Materials A phase I/II multicenter randomized clinical trial with active control was conducted. Thirty patients diagnosed with knee OA were randomly assigned to intraarticularly administered hyaluronic acid alone (control), or together with 10 × 10 6 or 100 × 10 6 cultured autologous BM-MSCs, and followed up for 12 months. Pain and function were assessed using VAS and WOMAC and by measuring the knee motion range. X-ray and magnetic resonance imaging analyses were performed to analyze joint damage. Results No adverse effects were reported after BM-MSC administration or during follow-up. BM-MSC-administered patients improved according to VAS during all follow-up evaluations and median value (IQR) for control, low-dose and high-dose groups change from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 4 (3, 5), 2 (1, 3) and 2 (0,4) respectively at 12 months (low-dose vs control group p = 0.005 and high-dose vs control group p < 0.009). BM-MSC-administered patients were also superior according to WOMAC, although improvement in control and low-dose patients could not be significantly sustained beyond 6 months. On the other hand, the BM-MSC high-dose group exhibited an improvement of 16.5 (12, 19) points at 12 months (p < 0.01). Consistent with WOMAC and VAS values, motion ranges remained unaltered in the control group but improved at 12 months with BM-MSCs. X-ray revealed a reduction of the knee joint space width in the control group that was not seen in BM-MSCs high-dose group. MRI (WORMS protocol) showed that joint damage decreased only in the BM-MSC high-dose group, albeit slightly. Conclusions The single intraarticular injection of in vitro expanded autologous BM-MSCs together with HA is a safe and feasible procedure that results in a clinical and functional improvement of knee OA, especially when 100 × 10 6 cells are administered. These results pave the way for a future phase III clinical trial. Clinical Trials.gov identifier NCT02123368. Nº EudraCT: 2009-017624-72

• Publisher: BioMed Central,BioMed Central Ltd
• Subject: Aged / Biomedical and Life Sciences / Biomedicine / Bone marrow / Care and treatment / Clinical translation / Clinical trials / Combined Modality Therapy / Demography / Female / Humans / Hyaluronic Acid - administration & dosage / Hyaluronic Acid - adverse effects / Hyaluronic Acid - pharmacology / Injections, Intra-Articular / Magnetic Resonance Imaging / Male / Medicine/Public Health / Mesenchymal Stem Cell Transplantation - adverse effects / Middle Aged / Osteoarthritis / Osteoarthritis, Knee - diagnostic imaging / Osteoarthritis, Knee - pathology / Osteoarthritis, Knee - physiopathology / Osteoarthritis, Knee - therapy / Range of Motion, Articular - drug effects / Stem cells / Transplantation / Treatment Outcome / Visual Analog Scale