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PMID: 20668554 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Microvesicles derived from adult human bone marrow and tissue specific mesenchymal stem cells shuttle selected pattern of miRNAs.

PloS one ·Vol. 5 ·No. 7 ·2010-07-27 ·Pages e11803

Collino F, Deregibus MC, Bruno S, Sterpone L, Aghemo G, Viltono L, Tetta C, Camussi G

Abstract

Cell-derived microvesicles (MVs) have been described as a new mechanism of cell-to-cell communication. MVs after internalization within target cells may deliver genetic information. Human bone marrow derived mesenchymal stem cells (MSCs) and liver resident stem cells (HLSCs) were shown to release MVs shuttling functional mRNAs. The aim of the present study was to evaluate whether MVs derived from MSCs and HLSCs contained selected micro-RNAs (miRNAs). MVs were isolated from MSCs and HLSCs. The presence in MVs of selected ribonucleoproteins involved in the traffic and stabilization of RNA was evaluated. We observed that MVs contained TIA, TIAR and HuR multifunctional proteins expressed in nuclei and stress granules, Stau1 and 2 implicated in the transport and stability of mRNA and Ago2 involved in miRNA transport and processing. RNA extracted from MVs and cells of origin was profiled for 365 known human mature miRNAs by real time PCR. Hierarchical clustering and similarity analysis of miRNAs showed 41 co-expressed miRNAs in MVs and cells. Some miRNAs were accumulated within MVs and absent in the cells after MV release; others were retained within the cells and not secreted in MVs. Gene ontology analysis of predicted and validated targets showed that the high expressed miRNAs in cells and MVs could be involved in multi-organ development, cell survival and differentiation. Few selected miRNAs shuttled by MVs were also associated with the immune system regulation. The highly expressed miRNAs in MVs were transferred to target cells after MV incorporation. This study demonstrated that MVs contained ribonucleoproteins involved in the intracellular traffic of RNA and selected pattern of miRNAs, suggesting a dynamic regulation of RNA compartmentalization in MVs. The observation that MV-highly expressed miRNAs were transferred to target cells, rises the possibility that the biological effect of stem cells may, at least in part, depend on MV-shuttled miRNAs. Data generated from this study, stimulate further functional investigations on the predicted target genes and pathways involved in the biological effect of human adult stem cells.

MeSH Terms
Blotting, Western Bone Marrow/metabolism Cells, Cultured Cytoplasmic Vesicles/metabolism Cytoskeleton/metabolism Humans In Situ Hybridization Mesenchymal Stem Cells/metabolism MicroRNAs/metabolism Reverse Transcriptase Polymerase Chain Reaction Ribonucleoproteins/metabolism Stem Cells/metabolism
Chemicals
MicroRNAs Ribonucleoproteins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Collino Federica
Department of Internal Medicine and Center for Molecular Biotechnology, University of Torino, Torino, Italy.
Deregibus Maria Chiara
Bruno Stefania
Sterpone Luca
Aghemo Giulia
Viltono Laura
Tetta Ciro
Camussi Giovanni
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0011803
Published
2010-07-27
Epub
2010-00-27
Pages
e11803
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2910725
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0011803 PMC Full Text View journal details
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