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Titolo Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury
Autore Stefano Gatti1,*, Stefania Bruno2,3,*, Maria Chiara Deregibus2, Andrea Sordi1, Vincenzo Cantaluppi2, Ciro Tetta4 and Giovanni Camussi2 1Center for Surgical Research, Fondazione IRCCS Ca` Granda Ospedale Maggiore Policlinico, Milano, Italy, 2Department of Internal Medicine and Molecular Biotechnology Center, University of Torino, Italy, 3Sis-Ter S.p.A., Palazzo Pignano, Crema, Italy and 4Fresenius Medical Care, Bad Homburg, Germany, UK Correspondence and offprint requests to: Giovanni Camussi
Referenza Nephrol Dial Transplant 2011; doi: 10.1093/ndt/gfr015
Contenuto Background. Several studies demonstrated that mesenchymal stem cells (MSCs) reverse acute kidney injury (AKI) by a paracrine mechanism rather than by MSC transdifferentiation. We recently demonstrated that microvesicles (MVs) released from MSCs may account for this paracrine mechanism by a horizontal transfer of messenger RNA and microRNA. Methods. MVs isolated from MSCs were injected intravenously in rats (30 lg/rat) immediately after monolateral nephrectomy and renal artery and vein occlusion for 45 min. To evaluate the MV effects on AKI induced by ischaemia-reperfusion injury (IRI), the animals were divided into different groups: normal rats (n ¼ 4), shamoperated rats (n ¼ 6), IRI rats (n¼ 6), IRI1MV rats (n ¼ 6), and IRI 1 RNase-MV rats (n ¼ 6), and all animals were sacrificed at Day 2 after the operation. To evaluate the chronic kidney damage consequent to IRI, the rats were divided into different groups: sham-operated rats (n ¼ 6) and IRI rats (n ¼ 6), IRI 1 MV rats (n ¼ 6), and all animal were sacrificed 6 months after the operation. Results. We found that a single administration of MVs, immediately after IRI, protects rats from AKI by inhibiting apoptosis and stimulating tubular epithelial cell proliferation. The MVs also significantly reduced the impairment of renal function. Pretreatment of MVs with RNase to inactivate their RNA cargo abrogated these protective effects. Moreover, MVs by reducing the acute injury also protected from later chronic kidney disease. Conclusion.MVs released fromMSCs protect from AKI induced by ischaemia reperfusion injury and from subsequent chronic renal damage. This suggest that MVs could be exploited as a potential new therapeutic approach.
Data 10.03.2011
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