Dataset Information

PTX-3 Secreted by Intra-Articular-Injected SMUP-Cells Reduces Pain in an Osteoarthritis Rat Model.

ABSTRACT: Mesenchymal stem cells (MSCs) are accessible, abundantly available, and capable of regenerating; they have the potential to be developed as therapeutic agents for diseases. However, concerns remain in their further application. In this study, we developed a SMall cell+Ultra Potent+Scale UP cell (SMUP-Cell) platform to improve whole-cell processing, including manufacturing bioreactors and xeno-free solutions for commercialization. To confirm the superiority of SMUP-Cell improvements, we demonstrated that a molecule secreted by SMUP-Cells is capable of polarizing inflammatory macrophages (M1) into their anti-inflammatory phenotype (M2) at the site of injury in a pain-associated osteoarthritis (OA) model. Lipopolysaccharide-stimulated macrophages co-cultured with SMUP-Cells expressed low levels of M1-phenotype markers (CD11b, tumor necrosis factor-α, interleukin-1α, and interleukin-6), but high levels of M2 markers (CD163 and arginase-1). To identify the paracrine action underlying the anti-inflammatory effect of SMUP-Cells, we employed a cytokine array and detected increased levels of pentraxin-related protein-3 (PTX-3). Additionally, PTX-3 mRNA silencing was applied to confirm PTX-3 function. PTX-3 silencing in SMUP-Cells significantly decreased their therapeutic effects against monosodium iodoacetate (MIA)-induced OA. Thus, PTX-3 expression in injected SMUP-Cells, applied as a therapeutic strategy, reduced pain in an OA model.

SUBMITTER: Lee M

PROVIDER: S-EPMC8466059 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Background/objectiveOxidative stress plays an important role in osteoarthritis (OA), causing inflammation and matrix degradation in joints. Previous studies have shown that antioxidants such as quercetin and vitamin C are potential candidates for treating OA. We aimed to determine whether a formulation of quercetin and vitamin C, together with an iron chelator, could retard OA progression in a post-traumatic OA rat model.MethodsTwelve rats received anterior cruciate ligament transection for OA induction. At 20 weeks postoperation, weekly intra-articular injection of 50 ?L of either saline or a formulation of quercetin dehydrate, sodium-L-ascorbate, and deferoxamine mesylate was given consecutively for 4 weeks (n = 5). Gait analysis was performed at pretreatment, and at 1 week and 5 weeks post-treatment. Microcomputed tomography scanning and histological scoring were performed at 5 weeks post-treatment.ResultsGait analysis showed that intra-articular injections of antioxidant formulation did not improve pain-associated Limb Idleness Index over time (p = 0.449, Friedman test). However, at 5 weeks post-treatment, the treatment group exhibited a significantly lower Limb Idleness Index than the control group (p = 0.047, Mann-Whitney U test). At 5 weeks post-treatment, microcomputed tomography analysis revealed that there was no difference in any parameter between the treatment and control groups (p > 0.05, Student t test). Severe OA histopathological changes were found in both groups. The Osteoarthritis Research Society International scores of the treatment and control groups were 20 (range, 20-26) and 20 (range, 9-26), respectively (p = 0.382, Mann-Whitney U test).ConclusionIntra-articular injection of an antioxidant formulation containing quercetin, vitamin C, and deferoxamine did not retard OA progression in advanced-stage OA. Future studies should aim to determine whether giving antioxidants in early OA, with prolonged drug retention, would be effective in retarding OA progression.

Dataset Information

PTX-3 Secreted by Intra-Articular-Injected SMUP-Cells Reduces Pain in an Osteoarthritis Rat Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets