Cited by 608Extracellular vesicles in diseaseMicroRNA in disease regulationMesenchymal stem cell research

Microvesicles Derived from Adult Human Bone Marrow and Tissue Specific Mesenchymal Stem Cells Shuttle Selected Pattern of miRNAs

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Collino, Federica, Deregibus, Maria Chiara, Bruno, Stefania, Sterpone, Luca, Aghemo, Giulia, Viltono, Laura, Tetta, Ciro, Camussi, Giovanni·2010·PLoS ONE

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.

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  • microRNA's presence in exosomes has been reported in different cells and cancer types.

    “microRNA's presence in exosomes have been already reported in different cells and cancer types (44–50).”

    From Potential Therapeutic Effects of Exosomes Packed With a miR-21-Sponge Construct in a Rat Model of Glioblastoma (2019) · cites this paper as [44]

    The Introduction (page not available) reports miRNAs in mast-cell exosomes and in microvesicles from several other cell sources, including the blood of patients with ovarian tumors. It does not establish their presence in exosomes across different cancer types; the tumor-related example concerns blood microvesicles, not identified cancer-cell exosomes. (LLM, conf=0.85)

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Research works printed but not linked: 64

  1. [1]Schorey JS Bhatnagar S 2008 Exosome function: from tumor immunology to pathogen biology. Traffic 9 871 881 18331451 PMC3636814
  2. [2]Skog J Wurdinger T van Rijn S Meijer DH Gainche L 2008 Glioblastoma microvesicles transport RNA and proteins that promote tumour growth and provide diagnostic biomarkers. Nat Cell Biol 10 1470 1476 19011622 PMC3423894
  3. [3]Ratajczak J Miekus K Kucia M Zhang J Reca R 2006 Embryonic stem cell-derived microvesicles reprogram hematopoietic progenitors: evidence for horizontal transfer of mRNA and protein delivery. Leukemia 20 847 856 16453000
  4. [4]Deregibus MC Cantaluppi V Calogero R Lo Iacono M Tetta C 2007 Endothelial progenitor cell derived microvesicles activate an angiogenic program in endothelial cells by a horizontal transfer of mRNA. Blood 110 2440 2448 17536014
  5. [5]Quesenberry PJ Aliotta JM 2008 The paradoxical dynamism of marrow stem cells: considerations of stem cells, niches, and microvesicles. Stem Cell Rev 4 137 147 18665337 PMC4495665
  6. [6]Aliotta JM Sanchez-Guijo FM Dooner GJ Johnson KW Dooner MS 2007 Alteration of marrow cell gene expression, protein production, and engraftment into lung by lung-derived microvesicles: a novel mechanism for phenotype modulation. Stem Cells 25 2245 2256 17556595 PMC3376082
  7. [7]Deregibus MC Tetta C Camussi G 2010 The dynamic stem cell microenvironment is orchestrated by microvesicle-mediated transfer of genetic information. Histol Histopathol 25 397 404 20054810
  8. [8]Bruno S Grange C Deregibus MC Calogero RA Saviozzi S 2009 Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J Am Soc Nephrol 20 1053 1067 19389847 PMC2676194
  9. [9]Herrera MB Bruno S Buttiglieri S Tetta C Gatti S 2006 Isolation and characterization of a stem cell population from adult human liver. Stem Cells 24 2840 2850 16945998
  10. [10]Herrera MB Fonsato V Gatti S Deregibus MC Sordi A 2009 Human liver stem cell-derived microvesicles accelerate hepatic regeneration in hepatectomized rats. J Cell Mol Med PMC3060338 19650833
  11. [11]Yuan A Farber EL Rapoport AL Tejada D Deniskin R 2009 Transfer of microRNAs by embryonic stem cell microvesicles. PLoS One 4 e4722 19266099 PMC2648987
  12. [12]Bartel DP 2004 MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116 281 297 14744438
  13. [13]Lagos-Quintana M Rauhut R Lendeckel W Tuschl T 2001 Identification of novel genes coding for small expressed RNAs. Science 294 853 858 11679670
  14. [14]Lau NC Lim LP Weinstein EG Bartel DP 2001 An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294 858 862 11679671
  15. [15]Valadi H Ekstrom K Bossios A Sjostrand M Lee JJ 2007 Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9 654 659 17486113
  16. [16]Hunter MP Ismail N Zhang X Aguda BD Lee EJ 2008 Detection of microRNA expression in human peripheral blood microvesicles. PLoS One 3 e3694 19002258 PMC2577891
  17. [17]Dahiya N Sherman-Baust CA Wang TL Davidson B Shih Ie M 2008 MicroRNA expression and identification of putative miRNA targets in ovarian cancer. PLoS One 3 e2436 18560586 PMC2410296
  18. [18]Chen TS Lai RC Lee MM Choo AB Lee CN 2010 Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs. Nucleic Acids Res 38 215 24 19850715 PMC2800221
  19. [19]Anderson P Kedersha N 2006 RNA granules. J Cell Biol 172 803 808 16520386 PMC2063724
  20. [20]Thomas MG Martinez Tosar LJ Loschi M Pasquini JM Correale J 2005 Staufen recruitment into stress granules does not affect early mRNA transport in oligodendrocytes. Mol Biol Cell 16 405 420 15525674 PMC539183
  21. [21]Hock J Meister G 2008 The Argonaute protein family. Genome Biol 9 210 18304383 PMC2374724
  22. [22]Doublier S Musante L Lupia E Candiano G Spatola T 2005 Direct effect of plasma permeability factors from patients with idiopatic FSGS on nephrin and podocin expression in human podocytes. Int J Mol Med 16 49 58 15942677
  23. [23]Mestdagh P Van Vlierberghe P De Weer A Muth D Westermann F 2009 A novel and universal method for microRNA RT-qPCR data normalization. Genome Biol 10 R64 19531210 PMC2718498
  24. [24]Bae S Ahn JH Park CW Son HK Kim KS 2009 Gene and microRNA expression signatures of human mesenchymal stromal cells in comparison to fibroblasts. Cell Tissue Res 335 565 573 19089456
  25. [25]Maere S Heymans K Kuiper M 2005 BiNGO: a Cytoscape plugin to assess overrepresentation of gene ontology categories in biological networks. Bioinformatics 21 3448 3449 15972284
  26. [27]Lee Y Kim M Han J Yeom KH Lee S 2004 MicroRNA genes are transcribed by RNA polymerase II. EMBO J 23 4051 4060 15372072 PMC524334
  27. [28]Meng F Henson R Wehbe-Janek H Ghoshal K Jacob ST 2007 MicroRNA-21 regulates expression of the PTEN tumor suppressor gene in human hepatocellular cancer. Gastroenterology 133 647 658 17681183 PMC4285346
  28. [29]Park JK Lee EJ Esau C Schmittgen TD 2009 Antisense inhibition of microRNA-21 or -221 arrests cell cycle, induces apoptosis, and sensitizes the effects of gemcitabine in pancreatic adenocarcinoma. Pancreas 38 e190 199 19730150
  29. [31]Ji Q Hao X Zhang M Tang W Yang M 2009 MicroRNA miR-34 inhibits human pancreatic cancer tumor-initiating cells. PLoS One 4 e6816 19714243 PMC2729376
  30. [32]Zhu W Shan X Wang T Shu Y Liu P 2010 miR-181b modulates multidrug resistance by targeting BCL2 in human cancer cell lines. Int J Cancer 20162574
  31. [33]Xia L Zhang D Du R Pan Y Zhao L 2008 miR-15b and miR-16 modulate multidrug resistance by targeting BCL2 in human gastric cancer cells. Int J Cancer 123 372 379 18449891
  32. [34]Zhou X Ren Y Moore L Mei M You Y 2010 Downregulation of miR-21 inhibits EGFR pathway and suppresses the growth of human glioblastoma cells independent of PTEN status. Lab Invest 90 144 155 20048743
  33. [35]Ratajczak J Wysoczynski M Hayek F Janowska-Wieczorek A Ratajczak MZ 2006 Membrane-derived microvesicles: important and underappreciated mediators of cell-to-cell communication. Leukemia 20 1487 1495 16791265
  34. [36]Heijnen HF Schiel AE Fijnheer R Geuze HJ Sixma JJ 1999 Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 94 3791 3799 10572093
  35. [37]Rozmyslowicz T Majka M Kijowski J Murphy SL Conover DO 2003 Platelet- and megakaryocyte-derived microparticles transfer CXCR4 receptor to CXCR4-null cells and make them susceptible to infection by X4-HIV. AIDS 17 33 42 12478067
  36. [38]Cocucci E Racchetti G Podini P Meldolesi J 2007 Enlargeosome traffic: exocytosis triggered by various signals is followed by endocytosis, membrane shedding or both. Traffic 8 742 757 17488290
  37. [39]Diamant M Tushuizen ME Sturk A Nieuwland R 2004 Cellular microparticles: new players in the field of vascular disease? Eur J Clin Invest 34 392 401 15200490
  38. [40]George JN Thoi LL McManus LM Reimann TA 1982 Isolation of human platelet membrane microparticles from plasma and serum. Blood 60 834 840 7115953
  39. [41]Martinez MC Tesse A Zobairi F Andriantsitohaina R 2005 Shed membrane microparticles from circulating and vascular cells in regulating vascular function. Am J Physiol Heart Circ Physiol 288 H1004 1009 15706036
  40. [42]Morel O Toti F Hugel B Freyssinet JM 2004 Cellular microparticles: a disseminated storage pool of bioactive vascular effectors. Curr Opin Hematol 11 156 164 15257014
  41. [43]Dooner MS Aliotta JM Pimentel J Dooner GJ Abedi M 2008 Conversion potential of marrow cells into lung cells fluctuates with cytokine-induced cell cycle. Stem Cells Dev 17 207 219 18447637
  42. [44]Gibbings DJ Ciaudo C Erhardt M Voinnet O 2009 Multivesicular bodies associate with components of miRNA effector complexes and modulate miRNA activity. Nat Cell Biol 11 1143 1149 19684575
  43. [45]Anderson P Kedersha N 2009 Stress granules. Curr Biol 19 R397 398 19467203
  44. [46]Ivanov PA Chudinova EM Nadezhdina ES 2003 Disruption of microtubules inhibits cytoplasmic ribonucleoprotein stress granule formation. Exp Cell Res 290 227 233 14567982
  45. [47]Moser JJ Fritzler MJ 2009 Cytoplasmic ribonucleoprotein (RNP) bodies and their relationship to GW/P bodies. Int J Biochem Cell Biol 42 828 43 19944184
  46. [48]Singh SR Hou SX 2008 Immunohistological techniques for studying the Drosophila male germline stem cell. Methods Mol Biol 450 45 59 18370050
  47. [49]Ballas N Grunseich C Lu DD Speh JC Mandel G 2005 REST and its corepressors mediate plasticity of neuronal gene chromatin throughout neurogenesis. Cell 121 645 657 15907476
  48. [50]Stadler BM Ruohola-Baker H 2008 Small RNAs: keeping stem cells in line. Cell 132 563 566 18295575 PMC2925130
  49. [51]Tay YM Tam WL Ang YS Gaughwin PM Yang H 2008 MicroRNA-134 modulates the differentiation of mouse embryonic stem cells, where it causes post-transcriptional attenuation of Nanog and LRH1. Stem Cells 26 17 29 17916804
  50. [52]Valtieri M Sorrentino A 2008 The mesenchymal stromal cell contribution to homeostasis. J Cell Physiol 217 296 300 18615579
  51. [53]Greco SJ Rameshwar P 2007 MicroRNAs regulate synthesis of the neurotransmitter substance P in human mesenchymal stem cell-derived neuronal cells. Proc Natl Acad Sci U S A 104 15484 15489 17855557 PMC2000543
  52. [54]Lakshmipathy U Hart RP 2008 Concise review: MicroRNA expression in multipotent mesenchymal stromal cells. Stem Cells 26 356 363 17991914 PMC2673465
  53. [55]Masaki S Ohtsuka R Abe Y Umemura T 2008 [Expression analysis of microRNAs in erythropoiesis]. Rinsho Byori 56 1086 1092 19175072
  54. [56]Dore LC Amigo JD Dos Santos CO Zhang Z Gai X 2008 A GATA-1-regulated microRNA locus essential for erythropoiesis. Proc Natl Acad Sci U S A 105 3333 3338 18303114 PMC2265118
  55. [57]Williams AE Moschos SA Perry MM Barnes PJ Lindsay MA 2007 Maternally imprinted microRNAs are differentially expressed during mouse and human lung development. Dev Dyn 236 572 580 17191223 PMC2582151
  56. [58]Bandres E Bitarte N Arias F Agorreta J Fortes P 2009 microRNA-451 regulates macrophage migration inhibitory factor production and proliferation of gastrointestinal cancer cells. Clin Cancer Res 15 2281 2290 19318487
  57. [59]Fazi F Rosa A Fatica A Gelmetti V De Marchis ML 2005 A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell 123 819 831 16325577
  58. [60]Johnnidis JB Harris MH Wheeler RT Stehling-Sun S Lam MH 2008 Regulation of progenitor cell proliferation and granulocyte function by microRNA-223. Nature 451 1125 1129 18278031
  59. [61]Wong QW Lung RW Law PT Lai PB Chan KY 2008 MicroRNA-223 is commonly repressed in hepatocellular carcinoma and potentiates expression of Stathmin1. Gastroenterology 135 257 269 18555017
  60. [62]Zernecke A Bidzhekov K Noels H Shagdarsuren E Gan L 2009 Delivery of microRNA-126 by apoptotic bodies induces CXCL12-dependent vascular protection. Sci Signal 2 ra81 19996457
  61. [63]Koh W Sheng CT Tan B Lee QY Kuznetsov V 2010 Analysis of deep sequencing microRNA expression profile from human embryonic stem cells derived mesenchymal stem cells reveals possible role of let-7 microRNA family in downstream targeting of hepatic nuclear factor 4 alpha. BMC Genomics 11 Suppl 1 S6 PMC2822534 20158877
  62. [65]Kedersha N Anderson P 2007 Mammalian stress granules and processing bodies. Methods Enzymol 431 61 81 17923231
  63. [66]Sterpone L Collino F Camussi GC L (forthcoming) Analysis and Clustering of MicroRNA Array: A New Efficient And Reliable Computational Method. Arabnia H Software Tools and Algorithms for Biological Systems (book series, Advances in Experimental Medicine and Biology, AEMB) Georgia: University of Georgia, Department of Computer Science Springer 21431609
  64. [67]Schmittgen TD Lee EJ Jiang J Sarkar A Yang L 2008 Real-time PCR quantification of precursor and mature microRNA. Methods 44 31 38 18158130 PMC2663046

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Authors
Collino, F., Deregibus, M. C., Bruno, S., Sterpone, L., Aghemo, G., Viltono, L., Tetta, C., & Camussi, G.
Affiliations
  • University of Turin (IT)
  • Politecnico di Torino (IT)
  • Fresenius Medical Care (Germany) (DE)
Corresponding author
Camussi, Giovanni
Venue
PLoS ONE
Published
2010-07-27
Volume
5
Issue
7
Pages
e11803
ISSN
1932-6203 (ISSN-L)
OpenAlex
W2108541168
Cited by
608
References
3
Citations by year
2026: 7 · 2025: 8 · 2024: 12 · 2023: 10 · 2022: 23 · 2021: 35 · 2020: 39 · 2019: 35 · 2018: 45 · 2017: 55 · 2016: 69 · 2015: 52 · 2014: 59 · 2013: 63 · 2012: 65
FWCI
20.73
Type
journal article
Language
en
Open access
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institutional Research Information System University of Turin (University of Turin) (submittedVersion, other-oa)
  • Padua Research Archive (University of Padova) (submittedVersion, cc-by)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Figshare (submittedVersion, cc-by)
  • PORTO@Iris (submittedVersion, cc-by)
  • PORTO Publications Open Repository TOrino (Politecnico di Torino) (submittedVersion)
Funders
  • Fresenius Medical Care North America
  • Associazione Italiana per la Ricerca sul Cancro
  • Regione Piemonte
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
microvesicles, mesenchymal stem cells, bone marrow, microRNA, extracellular vesicles, ribonucleoprotein, transient ischemic attack, TIAR, HuR, STAU1, STAU2, Argonaute 2, cell-to-cell communication, immune regulation
MeSH terms
Bone Marrow, Cells, Cultured, Cytoskeleton, Humans, Ribonucleoproteins, Stem Cells, Blotting, Western, In Situ Hybridization, Reverse Transcriptase Polymerase Chain Reaction, Cytoplasmic Vesicles, MicroRNAs, Mesenchymal Stem Cells

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