Osteoblasts secrete miRNA-containing extracellular vesicles that enhance expansion of human umbilical cord blood cells.

Abstract:

:Osteolineage cells represent one of the critical bone marrow niche components that support maintenance of hematopoietic stem and progenitor cells (HSPCs). Recent studies demonstrate that extracellular vesicles (EVs) regulate stem cell development via horizontal transfer of bioactive cargo, including microRNAs (miRNAs). Using next-generation sequencing we show that human osteoblast-derived EVs contain highly abundant miRNAs specifically enriched in EVs, including critical regulators of hematopoietic proliferation (e.g., miR-29a). EV treatment of human umbilical cord blood-derived CD34(+) HSPCs alters the expression of candidate miRNA targets, such as HBP1, BCL2 and PTEN. Furthermore, EVs enhance proliferation of CD34(+) cells and their immature subsets in growth factor-driven ex vivo expansion cultures. Importantly, EV-expanded cells retain their differentiation capacity in vitro and successfully engraft in vivo. These discoveries reveal a novel osteoblast-derived EV-mediated mechanism for regulation of HSPC proliferation and warrant consideration of EV-miRNAs for the development of expansion strategies to treat hematological disorders.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Morhayim J,van de Peppel J,Braakman E,Rombouts EW,Ter Borg MN,Dudakovic A,Chiba H,van der Eerden BC,Raaijmakers MH,van Wijnen AJ,Cornelissen JJ,van Leeuwen JP

doi

10.1038/srep32034

subject

Has Abstract

pub_date

2016-09-02 00:00:00

pages

32034

issn

2045-2322

pii

srep32034

journal_volume

6

pub_type

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