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

Jess Morhayim, Jeroen Van De Peppel, Eric Braakman, Elwin W.J.C. Rombouts, Mariette N.D. Ter Borg, Amel Dudakovic, Hideki Chiba, Bram C.J. Van Der Eerden, Marc H. Raaijmakers, Andre J. Van Wijnen, Jan J. Cornelissen, Johannes P. Van Leeuwen

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7 Scopus citations

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.

Original languageEnglish (US)
Article number32034
JournalScientific reports
Volume6
DOIs
StatePublished - Sep 2 2016

ASJC Scopus subject areas

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    Morhayim, J., Van De Peppel, J., Braakman, E., Rombouts, E. W. J. C., Ter Borg, M. N. D., Dudakovic, A., Chiba, H., Van Der Eerden, B. C. J., Raaijmakers, M. H., Van Wijnen, A. J., Cornelissen, J. J., & Van Leeuwen, J. P. (2016). Osteoblasts secrete miRNA-containing extracellular vesicles that enhance expansion of human umbilical cord blood cells. Scientific reports, 6, [32034]. https://doi.org/10.1038/srep32034