title: Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury.
abstract: 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 μg/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 = 4), sham-operated rats (n = 6), IRI rats (n = 6), IRI + MV rats (n = 6), and IRI + RNase-MV rats (n = 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 = 6) and IRI rats (n = 6), IRI + MV rats (n = 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.
  
  
  CONCLUSIONS
  MVs released from MSCs 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.
authors.affiliation: Center for Surgical Research, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gatti
authors.forename: Stefania
authors.initials: S
authors.lastname: Bruno
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Deregibus
authors.forename: Andrea
authors.initials: A
authors.lastname: Sordi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Cantaluppi
authors.forename: Ciro
authors.initials: C
authors.lastname: Tetta
authors.forename: Giovanni
authors.initials: G
authors.lastname: Camussi
mesh_terms: D058186:Acute Kidney Injury / Q000517:prevention & control*; D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D055252:Cell-Derived Microparticles; D002478:Cells, Cultured; D006801:Humans; D007676:Kidney Failure, Chronic / Q000517:prevention & control*; D007684:Kidney Tubules / Q000166:cytology / Q000378:metabolism; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*