Microvesicles Derived from Adult Human Bone Marrow and Tissue Specific Mesenchymal Stem Cells Shuttle Selected Pattern of miRNAs
Federica Collino,Maria Chiara Deregibus,Stefania Bruno,Luca Sterpone,Giulia Aghemo,Laura Viltono,Ciro Tetta,Giovanni Camussi +7 more
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TLDR
It was 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.Abstract:
Background: 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). Methodology/Principal Findings: 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. Conclusions: 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.read more
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Biological properties of extracellular vesicles and their physiological functions
María Yáñez-Mó,Pia Siljander,Zoraida Andreu,Apolonija Bedina Zavec,Francesc E. Borràs,Edit I. Buzás,Krisztina Buzas,Krisztina Buzas,Enriqueta Casal,Francesco Cappello,Joana Carvalho,Joana Carvalho,Eva Colas,Anabela Cordeiro da Silva,Anabela Cordeiro da Silva,Stefano Fais,Juan M. Falcón-Pérez,Irene M. Ghobrial,Bernd Giebel,Mario Gimona,Mario Gimona,Michael W. Graner,Ihsan Gursel,Mayda Gursel,Niels H. H. Heegaard,Niels H. H. Heegaard,An Hendrix,Peter Kierulf,Katsutoshi Kokubun,Maja Kosanović,Veronika Kralj-Iglič,Eva-Maria Krämer-Albers,Saara Laitinen,Cecilia Lässer,Thomas Lener,Thomas Lener,Erzsébet Ligeti,Aija Linē,Georg Lipps,Alicia Llorente,Jan Lötvall,Mateja Manček-Keber,Antonio Marcilla,María Mittelbrunn,Irina Nazarenko,Esther N. M. Nolte-‘t Hoen,Tuula A. Nyman,Lorraine O'Driscoll,Mireia Olivan,Carla Oliveira,Carla Oliveira,Éva Pállinger,Hernando A. del Portillo,Hernando A. del Portillo,Jaume Reventós,Jaume Reventós,Marina Rigau,Eva Rohde,Eva Rohde,Marei Sammar,Francisco Sánchez-Madrid,Nuno Santarém,Nuno Santarém,Katharina Schallmoser,Katharina Schallmoser,Marie Stampe Ostenfeld,Willem Stoorvogel,Roman Štukelj,Susanne G. van der Grein,M. Helena Vasconcelos,M. Helena Vasconcelos,Marca H. M. Wauben,Olivier De Wever +72 more
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TL;DR: Emerging principles of miRNA regulation of stress signaling pathways are reviewed and applied to the authors' understanding of the roles of miRNAs in disease.
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