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).

Autor: Lamo-Espinosa JM; Department of Orthopaedic Surgery and Traumatology, Clínica Universidad de Navarra, Pamplona, Spain., Mora G; Department of Orthopaedic Surgery and Traumatology, Clínica Universidad de Navarra, Pamplona, Spain., Blanco JF; Department of Orthopaedic Surgery and Traumatology, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain.; TerCel (Spanish Cell Therapy Network, Spanish National Institute of Health Carlos III), Madrid, Spain., Granero-Moltó F; Department of Orthopaedic Surgery and Traumatology, Clínica Universidad de Navarra, Pamplona, Spain.; TerCel (Spanish Cell Therapy Network, Spanish National Institute of Health Carlos III), Madrid, Spain.; Cell Therapy Area, Clínica Universidad de Navarra, Pamplona, Spain.; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain., Nuñez-Córdoba JM; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.; Division of Biostatistics, Research Support Service, Central Clinical Trials Unit, Clínica Universidad de Navarra, Pamplona, Spain.; Department of Preventive Medicine and Public Health, Medical School, University of Navarra, Pamplona, Spain., Sánchez-Echenique C; Department of Orthopaedic Surgery and Traumatology, Clínica Universidad de Navarra, Pamplona, Spain., Bondía JM; Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain., Aquerreta JD; Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain., Andreu EJ; TerCel (Spanish Cell Therapy Network, Spanish National Institute of Health Carlos III), Madrid, Spain.; Cell Therapy Area, Clínica Universidad de Navarra, Pamplona, Spain., Ornilla E; Department of Rheumatology, Clínica Universidad de Navarra, Pamplona, Spain., Villarón EM; TerCel (Spanish Cell Therapy Network, Spanish National Institute of Health Carlos III), Madrid, Spain.; Department of Hematology, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain.; Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Castilla y León, Salamanca, Spain., Valentí-Azcárate A; Department of Orthopaedic Surgery and Traumatology, Clínica Universidad de Navarra, Pamplona, Spain., Sánchez-Guijo F; TerCel (Spanish Cell Therapy Network, Spanish National Institute of Health Carlos III), Madrid, Spain.; Department of Hematology, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain.; Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Castilla y León, Salamanca, Spain., Del Cañizo MC; TerCel (Spanish Cell Therapy Network, Spanish National Institute of Health Carlos III), Madrid, Spain.; Department of Hematology, IBSAL-Hospital Universitario de Salamanca, Salamanca, Spain.; Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Castilla y León, Salamanca, Spain., Valentí-Nin JR; Department of Orthopaedic Surgery and Traumatology, Clínica Universidad de Navarra, Pamplona, Spain., Prósper F; TerCel (Spanish Cell Therapy Network, Spanish National Institute of Health Carlos III), Madrid, Spain. fprosper@unav.es.; Cell Therapy Area, Clínica Universidad de Navarra, Pamplona, Spain. fprosper@unav.es.; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain. fprosper@unav.es.; Department of Hematology, Clínica Universidad de Navarra, Avenida Pío XII 36, 31009, Pamplona, Navarra, Spain. fprosper@unav.es.
Jazyk: angličtina
Zdroj: Journal of translational medicine [J Transl Med] 2016 Aug 26; Vol. 14 (1), pp. 246. Date of Electronic Publication: 2016 Aug 26.
DOI: 10.1186/s12967-016-0998-2
Abstrakt: 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.
Databáze: MEDLINE
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