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.
Highlights
Extracellular vesicles (EVs) are secreted nano-sized cellular compartments that carry a specific biochemical cargo encompassing bioactive proteins, lipids and nucleic acids to regulate the function of recipient cells[1,2,3]
To characterize osteoblast-derived extracellular vesicles (EVs), SV-HFO cells were cultured for 12–14 days, and EVs were isolated from the conditioned medium by a series of ultracentrifugation steps
We focused initially on miR-29a, which is significantly enriched in osteoblast-EVs, because it is known to be involved in early stages of hematopoiesis as a regulator of self-renewal, survival and proliferation of Hematopoietic stem cells (HSCs) and HSPCs30
Summary
Extracellular vesicles (EVs) are secreted nano-sized cellular compartments that carry a specific biochemical cargo encompassing bioactive proteins, lipids and nucleic acids to regulate the function of recipient cells[1,2,3]. Recent studies indicate that EV-miRNAs have biological roles in the hematopoietic system indicating the importance of EV-mediated paracrine signalling in hematopoiesis[11,12]. Hematopoietic stem cells (HSCs) are multipotent cells responsible for constant blood supply by undergoing tightly regulated self-renewal, proliferation and differentiation into different mature blood cell types. Osteolineage cells, ranging from primitive mesenchymal cells to bone-forming mature osteoblasts, are thought to be important to maintain hematopoietic stem and progenitor cells (HSPCs)[15,16,17,18,19]. We previously reported the protein content of human osteoblast-derived EVs at different stages of differentiation and mineralization[22]. We elucidate the miRNA profile of EVs secreted from human pre-osteoblasts using next-generation sequencing. Our findings provide a foundation for the utilization of EVs as novel tools to modulate hematopoiesis for the development of suitable strategies to treat hematological disorders
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
