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

Luciana De Luca, Stefania Trino, Ilaria Laurenzana, Vittorio Simeon, Giovanni Calice, Stefania Raimondo, Marina Podesta, Michele Santodirocco, Lazzaro Di Mauro, Francesco La Rocca, Antonella Caivano, Annalisa Morano, Francesco Frassoni, Daniela Cilloni, Luigi del Vecchio, Pellegrino Musto

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)6676-6692
Number of pages17
JournalOncotarget
Volume7
Issue number6
DOIs
Publication statusPublished - 2016

Keywords

  • Extracellular vesicles
  • Mesenchymal stem cells
  • microRNAs
  • piRNAs
  • Umbilical cord blood stem cells

ASJC Scopus subject areas

  • Oncology

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