THU0061 EVALUATION OF SAFETY AND EVOLUTION OF OSTEOARTHRITIC JOINTS AFTER THE ADMINISTRATION OF HETEROLOGOUS MESENCHYMAL STROMAL CELLS IN AN ANIMAL MODEL
Authors: P. C. Sánchez-Pedreira, Á. Vela-Anero, N. Otero Queijas, M. Lorenzo Toja, A. Somaza Serantes, T. Hermida Gómez, F. J. Blanco
Journal: Annals of the Rheumatic Diseases (2020)

Background: One of the main osteoarthritis (OA) consequences is the cartilage loss. Nowadays there is not cure for the OA, so there is an intense research focused on finding a therapy to solve this problem. In this paradigm heterologous mesenchymal stromal cells (MSCH) rise as a solution. Different studies used them as a cellular therapy in order to regenerate damaged cartilage. Furthermore, MSCH have shown anti-inflammatory effects. Objectives: 1) Study the safety of a single intraarticular injection of MSCH derived from healthy canine fat tissue (adMSCH) in OA joints of dogs 2) Observe the evolution of functionality and range of articular mobility of these treated joints 6 months after the injection. Methods: adMSCH obtained (n=10) were phenotypically characterized by flow cytometry, including the Major Histocompatibility Complex type II (MHC-II). Those with the best morphology and growth (n=5) were used for the injection. The infiltrated dogs (n=7) met our inclusion/exclusion criteria. The adMSCH were injected in 11 joints by 1 million of cells/kilogram of weight. Before the infiltration we evaluated the joints (basal visit, BV), the vital signs and the animal pain by the owner (Visual Analogical Scale, VAS). The same data were collected one week after the infiltration (V1) and also studied the injected zone. Six months after treatment (V2), joint functionality and range of articular mobility were evaluated, also data of behavioural changes and pain observed by the owners. Results: All cells obtained were negative for the MHC-II (0.45 ± 0.32). Vital signs did not change between BV and V1. No dog suffered by severe inflammation of the injected joint. One of them during two days had difficulty to support the load in the posterior limbs, but at the third day it performed that without difficulty. Other dog suffered mild inflammation which was solved in two days. The other animals did not show any adverse effect after the infiltration. In the V1 none of them showed any inflammation in the joint. The pain evaluation by the owners showed that all dogs have less pain or it did not increase since BV. This indicate that after the infiltration the animals did not suffer a pain increase. Data collected in V2 showed that the joint functionality tend to improve, one of the items showing significant differences between BV and V2. The range of articular mobility did not have neither differences nor tendencies to the improvement (Table 1). Table 1. Functionality and range of articular mobility comparison between BV and V2. Visits column show the number of joints in that state Variable Answers Visits t-student (p-value) n BV V2 FUNCTIONALITY Load changes Normal 3 7 0.095 11 Change load 8 4 Support fingers 0 0 No support 0 0 Load changes when getting up Correctly 1 6 0.024* 11 Position modification 10 5 Difficulty to get up 0 0 No get up 0 0 Lameness in cold No lameness 1 2 0.062 11 Mild lameness 6 9 Intense lameness 4 0 No support 0 0 Lameness when warmed No lameness 1 3 0.106 11 Mild lameness 8 8 Intense lameness 2 0 No support 0 0 RANGE OF ARTICULAR MOBILITY Articular passive manual mobility Without pain 0 0 0.400 11 Mild pain 3 5 Raised pain 8 6 Disabling pain 0 0 Flexion limitation Total flexion 9 8 0.750 11 Mild limitation 1 2 Severe limitation 1 1 Extension limitation Total extension 0 3 0.749 11 Mild limitation 9 4 Severe limitation 2 4 *. Statistical significance stablished at P ≤ 0.05 Conclusion: The administration of adMSCH did not show adverse effects, rejection, infection or complications, only a probably of a mild inflammation in the treated zone. Also, joint functionality tends to improve, so these cells seem to have, at least, an anti-inflammatory effect into the OA joint. Acknowledgments: Special thanks to the owners of the dogs who participated in this study. Disclosure of Interests: Paula-Catarina Sánchez-Pedreira: None declared, Ángela Vela-Anero: None declared, Nuria Otero Queijas: None declared, María Lorenzo Toja: None declared, Andrés Somaza Serantes: None declared, Tamara Hermida Gómez: None declared, Francisco J. Blanco Grant/research support from: Sanofi-Aventis, Lilly, Bristol MS, Amgen, Pfizer, Abbvie, TRB Chemedica International, Glaxo SmithKline, Archigen Biotech Limited, Novartis, Nichi-iko pharmaceutical Co, Genentech, Jannsen Research &amp; Development, UCB Biopharma, Centrexion Theurapeutics, Celgene, Roche, Regeneron Pharmaceuticals Inc, Biohope, Corbus Pharmaceutical, Tedec Meiji Pharma, Kiniksa Pharmaceuticals, Ltd, Gilead Sciences Inc, Consultant of: Lilly, Bristol MS, Pfizer