Extracellular Vesicles Derived from Human Liver Stem Cells Attenuate Chronic Kidney Disease Development in an In Vivo Experimental Model of Renal Ischemia and Reperfusion Injury

International Journal of Molecular Sciences

Samuela De Rosa¹  Chiara Pasquino¹  Giovanni Camussi¹  Elena Ceccotti¹  Cristina Grange¹  Stefania Bruno¹  Giulia Chiabotto¹  Stefania Tritta²  Massimo Cedrino² 

[1] Department of Medical Sciences, University of Torino, 10126 Torino, Italy;Molecular Biotechnology Center, University of Torino, 10126 Torino, Italy;

关键词: acute kidney injury;    chronic kidney disease;    renal fibrosis;    epithelial-to-mesenchymal transition;   

DOI  :  10.3390/ijms23031485

来源: DOAJ

【 摘 要 】

The potential therapeutic effect of extracellular vesicles (EVs) that are derived from human liver stem cells (HLSCs) has been tested in an in vivo model of renal ischemia and reperfusion injury (IRI), that induce the development of chronic kidney disease (CKD). EVs were administered intravenously immediately after the IRI and three days later, then their effect was tested at different time points to evaluate how EV-treatment might interfere with fibrosis development. In IRI-mice that were sacrificed two months after the injury, EV- treatment decreased the development of interstitial fibrosis at the histological and molecular levels. Furthermore, the expression levels of pro-inflammatory genes and of epithelial–mesenchymal transition (EMT) genes were significantly reverted by EV-treatment. In IRI-mice that were sacrificed at early time points (two and three days after the injury), functional and histological analyses showed that EV-treatment induced an amelioration of the acute kidney injury (AKI) that was induced by IRI. Interestingly, at the molecular level, a reduction of pro-fibrotic and EMT-genes in sacrificed IRI-mice was observed at days two and three after the injury. These data indicate that in renal IRI, treatment with HLSC-derived EVs improves AKI and interferes with the development of subsequent CKD by modulating the genes that are involved in fibrosis and EMT.

【 授权许可】

Unknown