Preconditioned Mesenchymal Stromal Cell-Derived Extracellular Vesicles (EVs) Counteract Inflammaging.
Cansu GorgunChiara AfricanoMaria Chiara CiferriNadia BertolaDaniele ReverberiRodolfo QuartoSilvia RaveraRoberta TassoPublished in: Cells (2022)
Inflammaging is one of the evolutionarily conserved mechanisms underlying aging and is defined as the long-term consequence of the chronic stimulation of the innate immune system. As macrophages are intimately involved in initiating and regulating the inflammatory process, their dysregulation plays major roles in inflammaging. The paracrine factors, and in particular extracellular vesicles (EVs), released by mesenchymal stromal cells (MSCs) retain immunoregulatory effects on innate and adaptive immune responses. In this paper, we demonstrate that EVs derived from MSCs preconditioned with hypoxia inflammatory cytokines exerted an anti-inflammatory role in the context of inflammaging. In this study, macrophages isolated from aged mice presented elevated pro-inflammatory factor levels already in basal conditions compared to the young counterpart, and this pre-activation status increased when cells were challenged with IFN-γ. EVs were able to attenuate the age-associated inflammation, inducing a decrease in the expression of TNF-α, iNOS, and the NADase CD38. Moreover, we demonstrate that EVs counteracted the mitochondrial dysfunction that affected the macrophages, reducing lipid peroxidation and hindering the age-associated impairment of mitochondrial complex I activity, oxygen consumption, and ATP synthesis. These results indicate that preconditioned MSC-derived EVs might be exploited as new anti-aging therapies in a variety of age-related diseases.
Keyphrases
- immune response
- oxidative stress
- bone marrow
- mesenchymal stem cells
- induced apoptosis
- dendritic cells
- anti inflammatory
- stem cells
- rheumatoid arthritis
- toll like receptor
- type diabetes
- nitric oxide
- transcription factor
- endoplasmic reticulum stress
- metabolic syndrome
- adipose tissue
- cell proliferation
- fatty acid
- cell death
- insulin resistance
- long non coding rna