P132 - The Inflammatory/catabolic “Signature” of IL-1 β Primed sEVs on Osteoarthritis Joint Cells
The last decade has seen growing efforts to exploit the effects of Adipose Derived Stromal Cells (ADSCs) in the treatment of degenerative diseases, including osteoarthritis (OA), and recent findings have suggested that ADSC therapeutic ability is related to paracrine mechanisms. Thus, scientific interest has moved to the ADSC secretome focusing on Small Extracellular Vesicles (sEVs) which can act as “biological drug carriers”. However, the behaviour of sEVs could be affected by ADSC pathophysiology that therefore represents an important issue for clinical application.
The aim of this study was to evaluate the impact of ADSC inflammatory status on their secretome and the effects of the latter on articular tissues, focusing on chondrocytes and synoviocytes derived from OA joints.
Methods and Materials
ADSCs were obtained from adipose tissue harvested during regenerative treatments; chondrocytes and synoviocytes were isolated from tissues collected during knee arthroplasty. sEVs were collected from IL-1β treated ADSC by combining precipitation and size exclusion chromatography. sEVs were quantified, characterized, and administered to chondrocytes/synoviocytes in either monoculture or in co-culture. Gene expression and protein release of cytokines/chemokines, catabolic and inflammatory molecules were analyzed at 4 and 15 h. At the same experimental times, the p65 nuclear translocation was investigated to assess the NF-κB pathway.
Findings of this study demonstrated that the biological effects of ADSC secretome can be affected by the inflammatory environment. IL-1β primed sEVs were able to transfer NF-κB activation to chondrocytes and synoviocytes, inducing the transcription/release of inflammatory chemokines and cytokines, as well as the transcription of major cartilage catabolic enzymes.
Our findings, combined to those we recently published, underline that sEV nature and effects depend on the homeostatic or inflammatory/catabolic status of the ADSC source. Thus, for therapeutic purposes, ADSC should undergo careful characterization to avoid the transfer of an unwanted message that can further promote OA progression.