title: 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.
authors: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Jess
authors: J
authors: Morhayim
authors: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Jeroen
authors: J
authors: van de Peppel
authors: Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Eric
authors: E
authors: Braakman
authors: Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Elwin W J C
authors: EW
authors: Rombouts
authors: Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Mariette N D
authors: MN
authors: Ter Borg
authors: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
authors: Amel
authors: A
authors: Dudakovic
authors: Fukushima Medical University School of Medicine, Hikarigaoka, 960-1295, Fukushima, Japan.
authors: Hideki
authors: H
authors: Chiba
authors: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Bram C J
authors: BC
authors: van der Eerden
authors: Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Marc H
authors: MH
authors: Raaijmakers
authors: Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA.
authors: Andre J
authors: AJ
authors: van Wijnen
authors: Department of Hematology, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Jan J
authors: JJ
authors: Cornelissen
authors: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
authors: Johannes P
authors: JP
authors: van Leeuwen
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D000067128:Extracellular Vesicles / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005312:Fetal Blood / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D010006:Osteoblasts / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D035683:MicroRNAs