Editors' ChoiceHEMATOLOGY

Care packages for the bone marrow

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Science Translational Medicine  15 Jul 2020:
Vol. 12, Issue 552, eabd3612
DOI: 10.1126/scitranslmed.abd3612


Platelets secrete extracellular vesicles that can traffic to the bone marrow and stimulate megakaryopoiesis.

Platelets have long been thought to serve primarily as key actors that respond to bleeding and, with the help of fibrin and other clotting factors, form a physical plug at sites of disrupted epithelium. However, recent data suggest platelets may play a much more dynamic role systemically, including the modulation of other cell subsets. One of the means by which they do this is through release of microparticles called platelet-derived extracellular vesicles (PEVs). Inflammation leads to platelet activation and consequent release of PEVs, which in turn contribute to pathologic processes including autoimmunity and cancer.

French and colleagues recently studied whether PEVs released in the peripheral circulation may signal back to the bone marrow. They used a murine model in which mice deficient for the thrombopoietin receptor (and thus thrombocytopenic at baseline) were infused with wild-type fluorescently labeled platelets and stimulated with lipopolysaccharide (LPS). The authors found that, particularly after LPS stimulation, platelet-like particles from the infused platelets trafficked to the bone marrow, where they bound to megakaryocytes; similar findings were observed in another inflammatory model of murine autoimmunity. This binding of PEVs to megakaryocytes and potentially megakaryocytic precursors increased the percentage of bone marrow cells that were megakaryocytes, providing a functional implication of this PEV-bone marrow signaling axis. In pediatric patients in remission from acute lymphoblastic leukemia, extracellular vesicles were found at higher concentrations in the bone marrow compared with the peripheral blood, had a more activated phenotype, and seemed to be primarily platelet-derived, suggesting that PEVs in humans also may traffic to the bone marrow.

These signals from activated platelets back to the bone marrow may in part explain derangements in platelet numbers commonly seen during inflammatory or infectious conditions. Further research is needed to understand how platelets direct specific signals to particular hematologic cell subsets, whether these signals are truly platelet-derived or just a sampling of the regional plasma, and the downstream mechanisms that direct hematopoietic changes. The ultimate importance of this work will be in understanding how to effectively modulate these responses to control systemic inflammation or improve hematopoiesis in specific clinical circumstances.

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