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Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. This study investigates the therapeutic potential of secretome derived from adipose tissue mesenchymal stem cells (ASCs) in mitigating inflammation and promoting cartilage repair in an in vitro model of OA. Our in vitro model comprised chondrocytes inflamed with TNF. To assess the therapeutic potential of secretome, inflamed chondrocytes were treated with it and concentrations of pro-inflammatory cytokines, metalloproteinases (MMPs) and extracellular matrix markers were measured. In addition, secretome-treated chondrocytes were subject to a microarray analysis to determine which genes were upregulated and which were downregulated. Treating TNF-inflamed chondrocytes with secretome in vitro inhibits the NF - κB pathway, thereby mediating anti-inflammatory and anti-catabolic effects. Additional protective effects of secretome on cartilage are revealed in the inhibition of hypertrophy markers such as RUNX2 and COL10A1, increased production of COL2A1 and ACAN and upregulation of SOX9 . These findings suggest that ASC-derived secretome can effectively reduce inflammation, promote cartilage repair, and maintain chondrocyte phenotype. This study highlights the potential of ASC-derived secretome as a novel, non-cell-based therapeutic approach for OA, offering a promising alternative to current treatments by targeting inflammation and cartilage repair mechanisms.

Background Context: Mesenchymal stem cells (MSCs) secretome or conditioned medium (CM) is a complex cocktail of different molecules, some of which, particularly those contained in extracellular vesicles, already have proven therapeutic applications., Purpose: CM may well represent promising therapy for discogenic pain and the intention of this work is to assess its therapeutic potential using an in vitro model of this condition., Study Design: This is an experimental study., Methods: Our in vitro model comprised nucleus pulposus (NP) and annulus fibrosus (AF) cells inflamed with TNF. To assess the potential therapeutic value of CM and its components, extracellular vesicles (EVs) and soluble culture fraction (SF), cell inflammation took place under 3 different conditions: either in the presence of whole CM, isolated EVs or SF, and concentrations of pro-inflammatory cytokines, metalloproteinases (MMPs) and neurotrophic factors produced in all 3 cases were compared., Results: In the presence of whole CM, both in vitro gene expression by the NP and AF test cells and analysis of their protein content showed high modulatory effects on inflammation and MMP inhibition. The presence of EVs and SF showed similar but much smaller effects, and this was particularly marked in the case of NP cells., Conclusions: Our results show that, compared to EVs and SF, the presence of whole CM has the greatest positive effect on the modulation of pro-inflammatory and catabolic factors. These observations suggest that CM could protect against inflammation and the resulting intervertebral disc (IVD) degeneration that leads to discogenic pain., Clinical Significance: Many patients' expectations are not met by current non-operative and surgical treatments for discogenic low back pain. We propose the use of the MSCs secretome for assessing its potential as cell-free therapy to treat degenerative disc disease modulating the inflammatory response., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Mesenchymal stem cells (MSCs) are the subject of intense research as they are a potential therapeutic tool for several clinical applications. The new MSCs action models are focused on the use of MSC-derived secretome which contains several growth factors, cytokines, microRNAs, and extracellular vesicles such as exosomes. Exosomes have recently emerged as a component with great potential involved as mediators in cellular communication. The isolation and identification of exosomes has made it possible for them to be used in cell-free therapies. The purposes of this study are: (i) to detect exosomes released into adipose-derived MSC conditioned cell culture medium, (ii) to identify exosome morphology, and (iii) to carry out a complete characterization of said exosomes. Moreover, it is aimed at determining which method for exosome isolation would be best to use. Precipitation has been identified as a highly useful method of exosome isolation since it provides higher efficiency and purity values than other methods. A broad characterization of the exosomes present in the MSC-conditioned medium was also carried out. This work fills a gap in the existing literature on bioactive molecules which have attracted a great deal of interest due to their potential use in cellular therapies., (© 2020 Anatomical Society.)