Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial
Lamo-Espinosa JM (1,2), Mora G (1), Blanco JF (3), Granero-Moltó F (1,2), Núñez-Córdoba JM (4,5,6), López-Elío S (1), Andreu E (2), Sánchez-Guijo F (7), Aquerreta JD (8), Bondía JM (8), Valentí-Azcárate A (1), Del Consuelo Del Cañizo M (7), Villarón EM (7), Valentí-Nin JR (1), Prósper F (9,10).
(1) Department of Orthopaedic Surgery and Traumatology, Clínica Universidad de Navarra, Pamplona, Spain.
(2) Cell Therapy Area, Clínica Universidad de Navarra, Pamplona, Spain.
(3) Department of Traumatology, Complejo Hospitalario de Salamanca, Salamanca, Spain.
(4) Division of Biostatistics, Research Support Service, Central Clinical Trials Unit, University of Navarra Clinic, Pamplona, Spain.
(5) Department of Preventive Medicine and Public Health, Medical School, University of Navarra, Pamplona, Spain.
(6) Epidemiology and Public Health Area, Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
(7) Department of Hematology, Complejo Hospitalario de Salamanca, Salamanca, Spain.
(8) Department of Radiology, Clínica Universidad de Navarra, Pamplona, Spain.
(9) Cell Therapy Area, Clínica Universidad de Navarra, Pamplona, Spain.
(10) Department of Hematology, Clínica Universidad de Navarra, Pamplona, Spain.
Mesenchymal stromal cells (MSCs) are a promising option to treat knee osteoarthritis (OA). Their safety and usefulness have been reported in several short-term clinical trials but less information is available on the long-term effects of MSC in patients with osteoarthritis. We have evaluated patients included in our previous randomized clinical trial (CMM-ART, NCT02123368) to determine their long-term clinical effect.
A phase I/II multicenter randomized clinical trial with active control was conducted between 2012 and 2014. Thirty patients diagnosed with knee OA were randomly assigned to Control group, intraarticularly administered hyaluronic acid alone, or to two treatment groups, hyaluronic acid together with 10 × 106 or 100 × 106 cultured autologous bone marrow-derived MSCs (BM-MSCs), and followed up for 12 months. After a follow up of 4 years adverse effects and clinical evolution, assessed using VAS and WOMAC scorings are reported.
No adverse effects were reported after BM-MSCs administration or during the follow-up. BM-MSCs-administered patients improved according to VAS, median value (IQR) for Control, Low-dose and High-dose groups changed from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 7 (6, 7), 2 (2, 5) and 3 (3, 4), respectively at the end of follow up (Low-dose vs Control group, p = 0.01; High-dose vs Control group, p = 0.004). Patients receiving BM-MSCs also improved clinically according to WOMAC.
Control group showed an increase median value of 4 points (- 11;10) while Low-dose and High-dose groups exhibited values of - 18 (- 28;- 9) and - 10 (- 21;- 3) points, respectively (Low-dose vs Control group p = 0.043). No clinical differences between the BM-MSCs receiving groups were found.
Single intraarticular injection of in vitro expanded autologous BM-MSCs is a safe and feasible procedure that results in long-term clinical and functional improvement of knee OA.
CITATION J Transl Med. 2018 Jul 31;16(1):213. doi: 10.1186/s12967-018-1591-7