Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Therapeutic Potential of Adipose-Derived Mesenchymal Stem Cell Secretome in Osteoarthritis: A Comprehensive Study

Version 1 : Received: 18 September 2024 / Approved: 18 September 2024 / Online: 19 September 2024 (12:05:46 CEST)

How to cite: González-Cubero, E.; González-Fernández, M. L.; Esteban Blanco, M.; Pérez-Castrillo, S.; Pérez-Fernández, E.; Navasa, N.; Aransay, A. M.; Anguita, J.; Villar-Suárez, V. The Therapeutic Potential of Adipose-Derived Mesenchymal Stem Cell Secretome in Osteoarthritis: A Comprehensive Study. Preprints 2024, 2024091449. https://doi.org/10.20944/preprints202409.1449.v1 González-Cubero, E.; González-Fernández, M. L.; Esteban Blanco, M.; Pérez-Castrillo, S.; Pérez-Fernández, E.; Navasa, N.; Aransay, A. M.; Anguita, J.; Villar-Suárez, V. The Therapeutic Potential of Adipose-Derived Mesenchymal Stem Cell Secretome in Osteoarthritis: A Comprehensive Study. Preprints 2024, 2024091449. https://doi.org/10.20944/preprints202409.1449.v1

Abstract

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, COLX and increases in Col2a1 and ACAN production as well as the upregulation of Sox-9. 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.

Keywords

Mesenchymal stem cells; osteoarthritis; conditioned medium; secretome; inflammatory cytokines

Subject

Biology and Life Sciences, Biology and Biotechnology

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