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| Status |
Public on Jan 20, 2009 |
| Title |
Microvesicles derived from human mesenchymal stem cells protect against acute tubular injury |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Administration of exogenous mesenchymal stem cells (MSCs) has been shown to improve the recovery from acute kidney injury (AKI). It has been suggested that the beneficial effect of MSCs is related to the paracrine release of factors favouring proliferation of intrinsic epithelial cells survived to injury rather than to their trans-differentiation. However the factors involved remain to be determined. In the present study we demonstrated that microvesicles (MVs) derived from human bone marrow MSCs are able to stimulate in vitro proliferation and apoptosis resistance of tubular epithelial cells (TEC). In addition, MVs were found to accelerate in vivo the morphological and functional recovery of glycerol induced AKI in SCID mice by inducing TEC proliferation. The effect of MVs on the recovery of AKI was comparable to that of human MSC treatment. In vitro we found that the CD44 and beta1-integrin-dependent incorporation of MVs in TEC was required for their biological action. However, despite their internalization, RNase-treated MVs failed to induce in vitro apoptosis resistance and TEC proliferation, and in vivo recovery from AKI, suggesting an RNA-dependent biological effect. Microarray analysis and quantitative RT-PCR of MV-RNA extract indicated that MVs were shuttling a specific subset of cellular mRNA, such as mRNA associated with the mesenchymal differentiative phenotype and with several cell functions involved in the control of transcription, proliferation, apoptosis and cell immune regulation. These results suggest that MVs derived from MSCs may activate a proliferative program in TEC survived to injury in AKI by an horizontal transfer of mRNA.
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| Overall design |
Microarrays were used not to define the amount of mRNAs in the MVs but only to define which transcripts were present. Transcripts present in the MVs were defined as those characterized by a positive linear relation between the transcript signal detected by the microarray analysis and the amount of total RNA hybridized. This analysis was done hybridizing arrays with labelled-cRNA produced using three different concentrations of total RNA extracted from two independent preparations of MVs.
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| Contributor(s) |
Bruno S, Grange C, Calogero RA, Saviozzi S, Collino F, Morando L, Busca A, Bussolati B, Deregibus C, Tetta C, Camussi G |
| Citation(s) |
19389847, 20668554 |
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| Submission date |
Jul 25, 2008 |
| Last update date |
Feb 15, 2013 |
| Contact name |
Raffaele A Calogero |
| E-mail(s) |
raffaele.calogero@unito.it
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| Phone |
++39 0116706454
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| Organization name |
University of Torino
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| Department |
Molecular Biotechnology Center
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| Lab |
Bioinformatics and Genomics Unit
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| Street address |
Via Nizza 52
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| City |
Torino |
| State/province |
To |
| ZIP/Postal code |
10126 |
| Country |
Italy |
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| Platforms (1) |
| GPL6102 |
Illumina human-6 v2.0 expression beadchip |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA113707 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE12243_RAW.tar |
7.4 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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