Preconditioned Mesenchymal Stromal Cell-Derived Extracellular Vesicles (EVs) Counteract Inflammaging

被引:4
|
作者
Gorgun, Cansu [1 ]
Africano, Chiara [2 ]
Ciferri, Maria Chiara [1 ]
Bertola, Nadia [1 ]
Reverberi, Daniele [3 ]
Quarto, Rodolfo [1 ,4 ]
Ravera, Silvia [1 ]
Tasso, Roberta [1 ]
机构
[1] Univ Genoa, Dept Expt Med DIMES, I-16132 Genoa, Italy
[2] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet & Maternal, I-16132 Genoa, Italy
[3] IRCCS Osped Policlin San Martino, UO Mol Pathol, I-16132 Genoa, Italy
[4] IRCCS Osped Policlin San Martino, UO Cellular Oncol, I-16132 Genoa, Italy
关键词
inflammaging; extracellular vesicles; macrophages; mesenchymal stromal cells;
D O I
10.3390/cells11223695
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-gamma. EVs were able to attenuate the age-associated inflammation, inducing a decrease in the expression of TNF-alpha, 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.
引用
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页数:19
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