title: MiRNAs and piRNAs from bone marrow mesenchymal stem cell extracellular vesicles induce cell survival and inhibit cell differentiation of cord blood hematopoietic stem cells: a new insight in transplantation.
abstract: Hematopoietic stem cells (HSC), including umbilical cord blood CD34+ stem cells (UCB-CD34+), are used for the treatment of several diseases. Although different studies suggest that bone marrow mesenchymal stem cells (BM-MSC) support hematopoiesis, the exact mechanism remains unclear. Recently, extracellular vesicles (EVs) have been described as a novel avenue of cell communication, which may mediate BM-MSC effect on HSC. In this work, we studied the interaction between UCB-CD34+ cells and BM-MSC derived EVs. First, by sequencing EV derived miRNAs and piRNAs we found that EVs contain RNAs able to influence UCB-CD34+ cell fate. Accordingly, a gene expression profile of UCB-CD34+ cells treated with EVs, identified about 100 down-regulated genes among those targeted by EV-derived miRNAs and piRNAs (e.g. miR-27b/MPL, miR-21/ANXA1, miR-181/EGR2), indicating that EV content was able to modify gene expression profile of receiving cells. Moreover, we demonstrated that UCB-CD34+ cells, exposed to EVs, significantly changed different biological functions, becoming more viable and less differentiated. UCB-CD34+ gene expression profile also identified 103 up-regulated genes, most of them codifying for chemokines, cytokines and their receptors, involved in chemotaxis of different BM cells, an essential function of hematopoietic reconstitution. Finally, the exposure of UCB-CD34+ cells to EVs caused an increased expression CXCR4, paralleled by an in vivo augmented migration from peripheral blood to BM niche in NSG mice. This study demonstrates the existence of a powerful cross talk between BM-MSC and UCB-CD34+ cells, mediated by EVs, providing new insight in the biology of cord blood transplantation.
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Centro di Riferimento Oncologico della Basilicata (CROB), Rionero in Vulture, 85028 (PZ), Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: De Luca
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Centro di Riferimento Oncologico della Basilicata (CROB), Rionero in Vulture, 85028 (PZ), Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Trino
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Centro di Riferimento Oncologico della Basilicata (CROB), Rionero in Vulture, 85028 (PZ), Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Laurenzana
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Centro di Riferimento Oncologico della Basilicata (CROB), Rionero in Vulture, 85028 (PZ), Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Simeon
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Centro di Riferimento Oncologico della Basilicata (CROB), Rionero in Vulture, 85028 (PZ), Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Calice
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin 10126, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Raimondo
authors.affiliation: Stem Cell Center, S. Martino Hospital, Genova 16132, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Podestà
authors.affiliation: Transfusion Medicine Unit, Puglia Cord Blood Bank, IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 (FG), Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Santodirocco
authors.affiliation: Transfusion Medicine Unit, Puglia Cord Blood Bank, IRCCS-Casa Sollievo della Sofferenza, San Giovanni Rotondo, 71013 (FG), Italy.
authors.forename: Lazzaro
authors.initials: L
authors.lastname: Di Mauro
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Centro di Riferimento Oncologico della Basilicata (CROB), Rionero in Vulture, 85028 (PZ), Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: La Rocca
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Centro di Riferimento Oncologico della Basilicata (CROB), Rionero in Vulture, 85028 (PZ), Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Caivano
authors.affiliation: Laboratory of Preclinical and Translational Research, IRCCS-Centro di Riferimento Oncologico della Basilicata (CROB), Rionero in Vulture, 85028 (PZ), Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Morano
authors.affiliation: Laboratorio Cellule Staminali Post Natali e Terapie Cellulari, Giannina Gaslini Institute, Genova 16148, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Frassoni
authors.affiliation: Department of Clinical and Biological Sciences, University of Turin, Turin 10126, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cilloni
authors.affiliation: CEINGE-Biotecnologie Avanzate S.C.a R.L., Naples, 80145, Italy.|Department of Molecular Medicine and Medical Biotechnologies, Federico II University, Naples 80131, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Del Vecchio
authors.affiliation: Scientific Direction, IRCCS-Centro di Riferimento Oncologico Basilicata (CROB), Rionero in Vulture, 85028 (PZ), Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Musto
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002470:Cell Survival; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D016130:Immunophenotyping; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*; D014162:Transfection
chemical_list: D035683:MicroRNAs; D034741:RNA, Small Interfering
keywords: extracellular vesicles; mesenchymal stem cells; microRNAs; piRNAs; umbilical cord blood stem cells