Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury

Stefano Gatti, Stefania Bruno, Maria Chiara Deregibus, Andrea Sordi, Vincenzo Cantaluppi, Ciro Tetta, Giovanni Camussi

Research output: Contribution to journalArticle

425 Citations (Scopus)

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.Conclusion. 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.

Original languageEnglish
Pages (from-to)1474-1483
Number of pages10
JournalNephrology Dialysis Transplantation
Volume26
Issue number5
DOIs
Publication statusPublished - May 2011

Fingerprint

Adult Stem Cells
Mesenchymal Stromal Cells
Acute Kidney Injury
Reperfusion
Ischemia
Reperfusion Injury
Ribonucleases
Kidney
Cell Transdifferentiation
Renal Veins
Renal Artery
Transfer RNA
Nephrectomy
MicroRNAs
Chronic Renal Insufficiency
Epithelial Cells
Cell Proliferation

Keywords

  • acute kidney injury
  • chronic kidney disease
  • ischaemia-reperfusion injury
  • mesenchymal stem cells
  • microvesicles

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. / Gatti, Stefano; Bruno, Stefania; Deregibus, Maria Chiara; Sordi, Andrea; Cantaluppi, Vincenzo; Tetta, Ciro; Camussi, Giovanni.

In: Nephrology Dialysis Transplantation, Vol. 26, No. 5, 05.2011, p. 1474-1483.

Research output: Contribution to journalArticle

Gatti, Stefano ; Bruno, Stefania ; Deregibus, Maria Chiara ; Sordi, Andrea ; Cantaluppi, Vincenzo ; Tetta, Ciro ; Camussi, Giovanni. / Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. In: Nephrology Dialysis Transplantation. 2011 ; Vol. 26, No. 5. pp. 1474-1483.
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KW - acute kidney injury

KW - chronic kidney disease

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