title: Microvesicles from Mesenchymal Stromal Cells Are Involved in HPC-Microenvironment Crosstalk in Myelodysplastic Patients.
abstract: Exosomes/microvesicles (MVs) provide a mechanism of intercellular communication. Our hypothesis was that mesenchymal stromal cells (MSC) from myelodysplastic syndrome (MDS) patients could modify CD34+ cells properties by MVs. They were isolated from MSC from MDS patients and healthy donors (HD). MVs from 30 low-risk MDS patients and 27 HD were purified by ExoQuick-TC™ or ultracentrifugation and identified by transmission electron microscopy, flow cytometry (FC) and western blot for CD63. Incorporation of MVs into CD34+ cells was analyzed by FC, and confocal and fluorescence microscopy. Changes in hematopoietic progenitor cell (HPC) properties were assessed from modifications in microRNAs and gene expression in CD34+ cells as well as viability and clonogenic assays of CD34+ cells after MVs incorporation. Some microRNAs were overexpressed in MVs from patients MSC and two of them, miR-10a and miR-15a, were confirmed by RT-PCR. These microRNAs were transferred to CD34+ cells, modifying the expression of MDM2 and P53 genes, which was evaluated by RT-PCR and western blot. Finally, examining CD34+ cells properties after incorporation, higher cell viability (p = 0.025) and clonogenic capacity (p = 0.037) were observed when MVs from MDS patients were incorporated. In summary, we show that BM-MSC release MVs with a different cargo in MDS patients compared with HD. These structures are incorporated into HPC and modify their properties.
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.|Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.|Red Nacional de Terapia Celular (TerCel), Instituto Nacional de Salud Carlos III, Madrid, Spain.|IBSAL-Hospital Universitario Salamanca, Salamanca, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Muntión
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.|IBSAL-Hospital Universitario Salamanca, Salamanca, Spain.
authors.forename: Teresa L
authors.initials: TL
authors.lastname: Ramos
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.|Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.|Red Nacional de Terapia Celular (TerCel), Instituto Nacional de Salud Carlos III, Madrid, Spain.|IBSAL-Hospital Universitario Salamanca, Salamanca, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Diez-Campelo
authors.affiliation: Red Nacional de Terapia Celular (TerCel), Instituto Nacional de Salud Carlos III, Madrid, Spain.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Rosón
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.|Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.|Red Nacional de Terapia Celular (TerCel), Instituto Nacional de Salud Carlos III, Madrid, Spain.|Centro de Investigación del Cáncer-IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain.|IBSAL-Hospital Universitario Salamanca, Salamanca, Spain.
authors.forename: Luis Ignacio
authors.initials: LI
authors.lastname: Sánchez-Abarca
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.|Centro de Investigación del Cáncer-IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain.|National Medicines Institute, Warsaw, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Misiewicz-Krzeminska
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.|Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.|Red Nacional de Terapia Celular (TerCel), Instituto Nacional de Salud Carlos III, Madrid, Spain.|Centro de Investigación del Cáncer-IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain.|IBSAL-Hospital Universitario Salamanca, Salamanca, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Preciado
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.|IBSAL-Hospital Universitario Salamanca, Salamanca, Spain.
authors.forename: María-Eugenia
authors.initials: ME
authors.lastname: Sarasquete
authors.affiliation: Red Nacional de Terapia Celular (TerCel), Instituto Nacional de Salud Carlos III, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: de Las Rivas
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.|Centro de Investigación del Cáncer-IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain.|IBSAL-Hospital Universitario Salamanca, Salamanca, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.|Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.|Red Nacional de Terapia Celular (TerCel), Instituto Nacional de Salud Carlos III, Madrid, Spain.|Centro de Investigación del Cáncer-IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain.|IBSAL-Hospital Universitario Salamanca, Salamanca, Spain.
authors.forename: Fermín
authors.initials: F
authors.lastname: Sánchez-Guijo
authors.affiliation: Servicio de Hematología, Hospital Universitario de Salamanca, Salamanca, Spain.|Centro en Red de Medicina Regenerativa y Terapia Celular de Castilla y León, Salamanca, Spain.|Red Nacional de Terapia Celular (TerCel), Instituto Nacional de Salud Carlos III, Madrid, Spain.|Centro de Investigación del Cáncer-IBMCC (Universidad de Salamanca-CSIC), Salamanca, Spain.|IBSAL-Hospital Universitario Salamanca, Salamanca, Spain.
authors.forename: María-Consuelo
authors.initials: MC
authors.lastname: Del Cañizo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34; D002450:Cell Communication; D002470:Cell Survival; D060833:Cellular Microenvironment; D055354:Exosomes / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics / Q000378:metabolism*
chemical_list: D018952:Antigens, CD34; D035683:MicroRNAs
references.citation: Leukemia. 2009 Apr;23(4):664-72
references.pmid: 19151777
references.citation: Leuk Lymphoma. 2009 Nov;50(11):1854-9
references.pmid: 19883312
references.citation: Bioinformatics. 2009 Dec 15;25(24):3325-6
references.pmid: 19808880
references.citation: Nature. 2010 Apr 8;464(7290):852-7
references.pmid: 20305640
references.citation: J Cell Sci. 2010 May 15;123(Pt 10):1603-11
references.pmid: 20445011
references.citation: PLoS One. 2010;5(7):e11803
references.pmid: 20668554
references.citation: Cell Stem Cell. 2010 Nov 5;7(5):606-17
references.pmid: 21040902
references.citation: Am J Hematol. 2010 Dec;85(12):935-42
references.pmid: 20941782
references.citation: Cell Cycle. 2011 Oct 1;10(19):3257-62
references.pmid: 21957490
references.citation: Blood. 2011 Nov 17;118(20):5583-92
references.pmid: 21948175
references.citation: Nucleic Acids Res. 2012 Jan;40(Database issue):D222-9
references.pmid: 22135297
references.citation: Blood. 2012 Jan 19;119(3):756-66
references.pmid: 22031862
references.citation: Cancer Lett. 2012 Apr 28;317(2):136-43
references.pmid: 22240014
references.citation: Curr Pharm Des. 2012;18(22):3170-9
references.pmid: 22571695
references.citation: Haematologica. 2012 Aug;97(8):1218-24
references.pmid: 22371183
references.citation: Leuk Res. 2012 Oct;36(10):1300-3
references.pmid: 22784712
references.citation: Blood Rev. 2013 Jan;27(1):31-9
references.pmid: 23261067
references.citation: Stem Cells Dev. 2013 Mar 1;22(5):758-71
references.pmid: 23034046
references.citation: Haematologica. 2013 Mar;98(3):414-9
references.pmid: 22983574
references.citation: Methods Mol Biol. 2013;988:181-97
references.pmid: 23475720
references.citation: J Clin Invest. 2013 Apr;123(4):1542-55
references.pmid: 23454749
references.citation: Blood. 2013 May 9;121(19):3811-7
references.pmid: 23660859
references.citation: Int J Mol Sci. 2013;14(7):14240-69
references.pmid: 23839094
references.citation: Leukemia. 2013 Sep;27(9):1841-51
references.pmid: 23797473
references.citation: Cell Stem Cell. 2013 Sep 5;13(3):285-99
references.pmid: 23850243
references.citation: Epigenetics. 2013 Jun;8(6):561-70
references.pmid: 23760524
references.citation: Int J Mol Med. 2014 May;33(5):1055-63
references.pmid: 24573178
references.citation: Cancer Lett. 2014 May 28;347(1):29-37
references.pmid: 24513178
references.citation: Cancer Lett. 2014 Jun 28;348(1-2):71-6
references.pmid: 24657661
references.citation: Blood. 2014 Jul 24;124(4):555-66
references.pmid: 24928860
references.citation: Methods Mol Biol. 2015;1219:139-55
references.pmid: 25308267
references.citation: Stem Cell Res Ther. 2014;5(6):124
references.pmid: 25384729
references.citation: Haematologica. 2001 Oct;86(10):1038-45
references.pmid: 11602409
references.citation: J Biol Chem. 1997 Sep 5;272(36):22966-73
references.pmid: 9278461
references.citation: Cytotherapy. 2006;8(4):315-7
references.pmid: 16923606
references.citation: Nat Rev Cancer. 2007 Feb;7(2):118-29
references.pmid: 17251918
references.citation: Blood. 2007 Mar 15;109(6):2630-3
references.pmid: 17105817
references.citation: Nat Cell Biol. 2007 Jun;9(6):654-9
references.pmid: 17486113
references.citation: Stem Cells. 2007 Sep;25(9):2245-56
references.pmid: 17556595
references.citation: Transfus Apher Sci. 2007 Oct;37(2):145-56
references.pmid: 17983836
references.citation: Curr Protoc Cell Biol. 2006 Apr;Chapter 3:Unit 3.22
references.pmid: 18228490
references.citation: Blood. 2008 May 15;111(10):4841-51
references.pmid: 18467609
references.citation: Leuk Res. 2008 Sep;32(9):1407-16
references.pmid: 18405968
references.citation: Methods Mol Biol. 2008;484:79-93
references.pmid: 18592174
references.citation: PLoS One. 2009;4(3):e4722
references.pmid: 19266099