Small Extracellular Vesicles from Inflamed Adipose Derived Stromal Cells Enhance the NF-κB-Dependent Inflammatory/Catabolic Environment of Osteoarthritis
The last decade has seen exponentially growing efforts to exploit the effects of adipose derived stromal cells (ADSC) in the treatment of a wide range of chronic degenerative diseases, including osteoarthritis (OA), the most prevalent joint disorder. In the perspective of developing a cell-free adva...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Stem Cells International |
| Online Access: | http://dx.doi.org/10.1155/2022/9376338 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832565311787761664 |
|---|---|
| author | Carola Cavallo Giulia Merli Nicoletta Zini Stefania D’Adamo Luca Cattini Michele Guescini Brunella Grigolo Alessandro Di Martino Spartaco Santi Rosa Maria Borzì Giuseppe Filardo |
| author_facet | Carola Cavallo Giulia Merli Nicoletta Zini Stefania D’Adamo Luca Cattini Michele Guescini Brunella Grigolo Alessandro Di Martino Spartaco Santi Rosa Maria Borzì Giuseppe Filardo |
| author_sort | Carola Cavallo |
| collection | DOAJ |
| description | The last decade has seen exponentially growing efforts to exploit the effects of adipose derived stromal cells (ADSC) in the treatment of a wide range of chronic degenerative diseases, including osteoarthritis (OA), the most prevalent joint disorder. In the perspective of developing a cell-free advanced therapy medicinal product, a focus has been recently addressed to the ADSC secretome that lends itself to an allogeneic use and can be further dissected for the selective purification of small extracellular vesicles (sEVs). sEVs can act as “biological drug carriers” to transfer information that mirror the pathophysiology of the providing cells. This is important in the clinical perspective where many OA patients are also affected by the metabolic syndrome (MetS). ADSC from MetS OA patients are dysfunctional and “inflammatory” primed within the adipose tissue. To mimic this condition, we exposed ADSC to IL-1β, and then we investigated the effects of the isolated sEVs on chondrocytes and synoviocytes, either cultured separately or in co-culture, to tease out the effects of these “IL-1β primed sEVs” on gene and protein expression of major inflammatory and catabolic OA markers. In comparison with sEVs isolated from unstimulated ADSC, the IL-1β primed sEVs were able to propagate NF-κB activation in bystander joint cells. The effects were more prominent on synoviocytes, possibly because of a higher expression of binding molecules such as CD44. These findings call upon a careful characterization of the “inflammatory fingerprint” of ADSC to avoid the transfer of an unwanted message as well as the development of in vitro “preconditioning” strategies able to rescue the antiinflammatory/anticatabolic potential of ADSC-derived sEVs. |
| format | Article |
| id | doaj-art-7e79d240fb6f4c7f83adf04f89ddac4a |
| institution | Kabale University |
| issn | 1687-9678 |
| language | English |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Stem Cells International |
| spelling | doaj-art-7e79d240fb6f4c7f83adf04f89ddac4a2025-02-03T01:08:47ZengWileyStem Cells International1687-96782022-01-01202210.1155/2022/9376338Small Extracellular Vesicles from Inflamed Adipose Derived Stromal Cells Enhance the NF-κB-Dependent Inflammatory/Catabolic Environment of OsteoarthritisCarola Cavallo0Giulia Merli1Nicoletta Zini2Stefania D’Adamo3Luca Cattini4Michele Guescini5Brunella Grigolo6Alessandro Di Martino7Spartaco Santi8Rosa Maria Borzì9Giuseppe Filardo10Laboratorio RAMSESApplied and Translational Research Center (ATRc)CNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”Department of Medical and Surgical SciencesLaboratorio di Immunoreumatologia e Rigenerazione TissutaleDepartment of Biomolecular ScienceLaboratorio RAMSESClinica Ortopedica e Traumatologica 2CNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”Laboratorio di Immunoreumatologia e Rigenerazione TissutaleApplied and Translational Research Center (ATRc)The last decade has seen exponentially growing efforts to exploit the effects of adipose derived stromal cells (ADSC) in the treatment of a wide range of chronic degenerative diseases, including osteoarthritis (OA), the most prevalent joint disorder. In the perspective of developing a cell-free advanced therapy medicinal product, a focus has been recently addressed to the ADSC secretome that lends itself to an allogeneic use and can be further dissected for the selective purification of small extracellular vesicles (sEVs). sEVs can act as “biological drug carriers” to transfer information that mirror the pathophysiology of the providing cells. This is important in the clinical perspective where many OA patients are also affected by the metabolic syndrome (MetS). ADSC from MetS OA patients are dysfunctional and “inflammatory” primed within the adipose tissue. To mimic this condition, we exposed ADSC to IL-1β, and then we investigated the effects of the isolated sEVs on chondrocytes and synoviocytes, either cultured separately or in co-culture, to tease out the effects of these “IL-1β primed sEVs” on gene and protein expression of major inflammatory and catabolic OA markers. In comparison with sEVs isolated from unstimulated ADSC, the IL-1β primed sEVs were able to propagate NF-κB activation in bystander joint cells. The effects were more prominent on synoviocytes, possibly because of a higher expression of binding molecules such as CD44. These findings call upon a careful characterization of the “inflammatory fingerprint” of ADSC to avoid the transfer of an unwanted message as well as the development of in vitro “preconditioning” strategies able to rescue the antiinflammatory/anticatabolic potential of ADSC-derived sEVs.http://dx.doi.org/10.1155/2022/9376338 |
| spellingShingle | Carola Cavallo Giulia Merli Nicoletta Zini Stefania D’Adamo Luca Cattini Michele Guescini Brunella Grigolo Alessandro Di Martino Spartaco Santi Rosa Maria Borzì Giuseppe Filardo Small Extracellular Vesicles from Inflamed Adipose Derived Stromal Cells Enhance the NF-κB-Dependent Inflammatory/Catabolic Environment of Osteoarthritis Stem Cells International |
| title | Small Extracellular Vesicles from Inflamed Adipose Derived Stromal Cells Enhance the NF-κB-Dependent Inflammatory/Catabolic Environment of Osteoarthritis |
| title_full | Small Extracellular Vesicles from Inflamed Adipose Derived Stromal Cells Enhance the NF-κB-Dependent Inflammatory/Catabolic Environment of Osteoarthritis |
| title_fullStr | Small Extracellular Vesicles from Inflamed Adipose Derived Stromal Cells Enhance the NF-κB-Dependent Inflammatory/Catabolic Environment of Osteoarthritis |
| title_full_unstemmed | Small Extracellular Vesicles from Inflamed Adipose Derived Stromal Cells Enhance the NF-κB-Dependent Inflammatory/Catabolic Environment of Osteoarthritis |
| title_short | Small Extracellular Vesicles from Inflamed Adipose Derived Stromal Cells Enhance the NF-κB-Dependent Inflammatory/Catabolic Environment of Osteoarthritis |
| title_sort | small extracellular vesicles from inflamed adipose derived stromal cells enhance the nf κb dependent inflammatory catabolic environment of osteoarthritis |
| url | http://dx.doi.org/10.1155/2022/9376338 |
| work_keys_str_mv | AT carolacavallo smallextracellularvesiclesfrominflamedadiposederivedstromalcellsenhancethenfkbdependentinflammatorycatabolicenvironmentofosteoarthritis AT giuliamerli smallextracellularvesiclesfrominflamedadiposederivedstromalcellsenhancethenfkbdependentinflammatorycatabolicenvironmentofosteoarthritis AT nicolettazini smallextracellularvesiclesfrominflamedadiposederivedstromalcellsenhancethenfkbdependentinflammatorycatabolicenvironmentofosteoarthritis AT stefaniadadamo smallextracellularvesiclesfrominflamedadiposederivedstromalcellsenhancethenfkbdependentinflammatorycatabolicenvironmentofosteoarthritis AT lucacattini smallextracellularvesiclesfrominflamedadiposederivedstromalcellsenhancethenfkbdependentinflammatorycatabolicenvironmentofosteoarthritis AT micheleguescini smallextracellularvesiclesfrominflamedadiposederivedstromalcellsenhancethenfkbdependentinflammatorycatabolicenvironmentofosteoarthritis AT brunellagrigolo smallextracellularvesiclesfrominflamedadiposederivedstromalcellsenhancethenfkbdependentinflammatorycatabolicenvironmentofosteoarthritis AT alessandrodimartino smallextracellularvesiclesfrominflamedadiposederivedstromalcellsenhancethenfkbdependentinflammatorycatabolicenvironmentofosteoarthritis AT spartacosanti smallextracellularvesiclesfrominflamedadiposederivedstromalcellsenhancethenfkbdependentinflammatorycatabolicenvironmentofosteoarthritis AT rosamariaborzi smallextracellularvesiclesfrominflamedadiposederivedstromalcellsenhancethenfkbdependentinflammatorycatabolicenvironmentofosteoarthritis AT giuseppefilardo smallextracellularvesiclesfrominflamedadiposederivedstromalcellsenhancethenfkbdependentinflammatorycatabolicenvironmentofosteoarthritis |