AB0101 Mesenchymal stem cells derived from bone marrow, umbilical cord and adipose tissue do not have the same effect on human osteoarthritic cartilage

• Published in: Annals of the rheumatic diseases Vol. 77; no. Suppl 2; p. 1246
• Main Authors: Alaaeddoine, N., saliba, N., moussa, M., hilal, G., khalil, C., haykal, G.
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group LTD 01.06.2018
• Subjects: ADAM protein; Adipose tissue; Arthritis; Arthroplasty (knee); Autografts; Autophagy; Bone marrow; Bone marrow transplantation; Cartilage diseases; CCL20 protein; Cell culture; Cell proliferation; Chondrocytes; Collagen; Collagenase 3; Cyclooxygenase-2; Degeneration; Enzyme-linked immunosorbent assay; Flow cytometry; Interleukin 6; Joint surgery; Knee; Lymphocytes B; Mesenchymal stem cells; Mesenchyme; Phagocytosis; Polymerase chain reaction; Stem cells; Umbilical cord
• ISSN: 0003-4967; 1468-2060
• DOI: 10.1136/annrheumdis-2018-eular.1747

BackgroundOsteoarthritis is a chronic debilitating disease characterised by degeneration of cartilage, synovitis and osteophytes formation.1 This disease does not only affect aged people but it afflicts also young athletes where until today no medications has proven efficacy in stopping the progression of the disease and/or regenerate the loss of cartilage.2 Recently cell therapy has attracted attention in many medical fields and especially in rheumatology and orthopaedic specialty. Stem cells due to their differentiation capacity, trophic and paracrine effects have been shown to serve as promising new modality in treating osteoarthritis.3,4 ObjectivesOur objective in this study is to investigate the effect and mechanism of action of the three sources of stem cells; bone marrow derived stem cells (B-MSC), adipose derived stem cells (A-MSC) and umbilical cord stem cells (U-MSC) on osteoarthritic chondrocytes.MethodsMesenchymal stem cells were isolated from bone marrow, adipose tissue and umbilical cord from 5 different donors respectively and cocultured with human osteoarthritic chondrocytes obtained from 5 patients undergoing total knee arthroplasty. The effect autophagy was determined using flow cytometry analysis. Quantitative polymerase chain reaction (qPCR) and ELISA were used to measure the changes in the major factors playing a role in OA such as(a disintegrin and metalloproteinase with thrombospondin motifs-5(ADAMDTS-5), Metalloproteinases (MMP-3, MMP13), tissue inhibitor of metalloproteinases (TIMP-1–2–3), Collagen, Cox-2, Il-6, the regulators of autophahy FOXO1, FOXO3, and LC3II and Beclin I in the tissues and cocultured media.ResultsIn our study we found that the three stem cells sources increased significantly the proliferation of chondrocytes, and increased autophagy via increasing Beclin 1 and LC3II, along with its regulators FOXO1, FOXO3 in human osteoarthritic chondrocytes with p<0.05. Furthermore, the three sources of stem cells caused a dose dependent significant decrease in MMP-3, MMP-13, ADAMTS-5, IL-6, CCL20 and COX-2 with p<0.05. Aggregan, collagen, TIMPs were also significantly increased by the co-culture of A-MSC, B-MSC, U-MSC.ConclusionsThese results suggest that stem cells could be a promising therapeutic target for the treatment of osteoarthritis.References[1] Soler R, et al. Final results of a phase I-II trial using ex vivo expanded autologous mesenchymal stromal cells for the treatment of osteoarthritis of the knee confirming safety and suggesting cartilage regeneration. Knee2016;23(4):647–6541.[2] Lagorce T, Buxeraud J, Guillot X. Comprendre l’arthrose. Actual Pharm2016Apr;55(555):18–22.[3] Martel-Pelletier J, Wildi LM, Pelletier J-P. Future therapeutics for osteoarthritis. Bone2012Aug;51(2):297–311.[4] Orozco L, Munar A, Soler R, Alberca M, Soler F, Huguet M, et al. Treatment of knee osteoarthritis with autologous mesenchymal stem cells: A pilot study. Transplantation2013Jun 27;95(12):1535–41.[5] Soler R, et al. Final results of a phase I-II trial using ex vivo expanded autologous mesenchymal stromal cells for the treatment of osteoarthritis of the knee confirming safety and suggesting cartilage regeneration. Knee2016;23(4):647–654.Disclosure of InterestNone declared