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• W2801370421 abstract "Purpose: Mesenchymal stem cells (MSCs) represent a promising biological therapeutic option as an OA modifying treatment and have shown clinical improvement. Next to their differentiation potential into several lineages, they have the ability to influence their environment by secreting trophic mediators. These secreted factors could possibly counteract inflammatory and catabolic processes and attract endogenous repair cells. By using the MSC secretome as an OA treatment instead of the MSCs themselves, the possibilities to provide a more standardized and affordable therapeutic option would be largely increased. Together with a decrease of legal and safety issues, this would greatly enhance the clinical applicability of cell-based treatment as a true disease modifying anti-osteoarthritic drug. Aim of our study was to explore the anti-osteoarthritic effects of MSC secretome on pain, subchondral bone changes, cartilage damage, synovial thickness and synovial macrophage subtypes in a mouse osteoarthritis model. Methods: For the production of MSC Conditioned Medium (MSC-CM), human bone marrow derived MSCs from 3 donors were stimulated with IFNγ and TNFα (50 ng/mL each). After 24 hours of stimulation, medium was replaced by αMem without Phenol Red containing 0.05% BSA. This medium was collected after 24 hours, concentrated using 3k cut-off filters, frozen and designated MSC-CM. OA was induced unilaterally in 54 male C57/Bl6 mice by two intra-articular collagenase injections (collagenase-induced osteoarthritis model). After 7 days, mice were randomly assigned to 3 consecutive injections with 20.000 MSCs, MSC-CM from 20.000 MSCs or medium only (control). Weight distribution over the left and right hind limbs was evaluated as an indicator of pain using an incapitance tester. Other outcome measures were evaluated by histology at 5 and 21 days after treatment. Results: Seven days after induction of OA (day 0), 41.2 6.3% of weight was distributed on the affected limb, indicating pain when compared to before OA (Fig. 1, P<0.0001). We observed an early normalization in weight bearing in MSC-CM injected animals at day 7 compared to day 0, indicating early pain reduction (P = 0.001). Moreover, mice that received MSC-CM displayed significantly less pain compared to the medium control at day 7 (P = 0.001). OA induction lead to loss of subchondral bone tissue in the medial tibia plateau, 5 days after the first collagenase injection. (Fig. 2, P = 0.003). The percentage of subchondral bone in the MSC-CM treated group as well as the MSC treated group was not statistically different from the healthy control group, indicating amelioration of OA related decrease of subchondral bone volume. No treatment effects were seen on cartilage damage, synovial inflammation or the presence of iNOS, CD206, or CD163 positive macrophages (Fig. 3A–C). Conclusions: In this study, we found that injection of human MSC secretome resulted in an early pain reduction and amelioration of early subchondral bone changes, in a comparable manner to injection of MSCs themselves. Possibly, these two aspects are related, since subchondral bone marrow edema or bone marrow lesions have clinically been shown to be correlated with patients perceived degree of pain. Synovitis is another OA feature which has clinically been related to pain. We did not find a treatment effect on synovial thickness or macrophage phenotype in our study. Additional studies are warranted to further unravel the mechanisms behind the therapeutic effects of MSCs and their secretome. This way, we can evolve this biological approach towards a true disease modifying anti-osteoarthritic drug, in which the use of secretome would greatly enhance the standardization, affordability and clinical translatability." @default.
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• W2801370421 date "2018-04-01" @default.
• W2801370421 modified "2023-09-27" @default.
• W2801370421 title "Mesenchymal stem cell secretome reduces pain and subchondral bone alterations in a mouse osteoarthritis model" @default.
• W2801370421 doi "https://doi.org/10.1016/j.joca.2018.02.049" @default.
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