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    Oral Communication

    Platelets and Megakaryocytes

    Platelet Production from Megakaryocytes

    OC 39.2 - Megakaryocytes derived from human CD34+ cells express and release Brain-Derived Neurotrophic Factor

    Monday, June 26, 2023
    11:00 – 11:15 ET
    Room: 515
    Session Available As: On-Demand
    Background: The brain-derived neurotrophic factor (BDNF) has been initially discovered in the brain, where its responsible for neurite survival and synaptic plasticity. Surprisingly, BDNF also induces platelet activation, secretion, and aggregation in human washed platelets and, more importantly, BDNF is also stored in platelets in concentrations reaching 100-1000-fold those of neurons. The origin of such levels of BDNF is debated. In this study, we investigate the hypothesis that BDNF in platelet is of megakaryocytic origin.

    Aims: We investigated BDNF expression in human CD34+-derived megakaryocytes, BDNF release during megakaryopoiesis and the effect of BDNF on megakaryocyte maturation.

    Methods: Mature megakaryocytes were derived from a 14-day culture of CD34+ cells isolated from adult peripheral blood. BDNF expression in megakaryocytes was assessed by western blotting, flow cytometry, q-PCR and ELISA. BDNF, its precursor proBDNF, as well as their receptors TrkB and p75NTR were also assessed. BDNF and proBDNF release from megakaryocytes at different stages of megakaryopoiesis were measured by ELISA. Megakaryocytes were treated with BDNF or/and BDNF inhibitors during differentiation and maturation stages. The study received ethical approval and all participants gave informed consent.

    Results: BDNF, proBDNF and their receptors TrkB and p75NTR were all expressed in CD34+-derived human megakaryocytes both at early (day 7 of culture) and late (day 14) stages of maturation. BDNF was released from mature megakaryocytes, whereas proBDNF was released from immature megakaryocytes. Addition of exogenous BDNF had no effect on the expansion or differentiation of CD34+ cells into megakaryocytes.

    Conclusion(s): BDNF was expressed in megakaryocytes derived from peripheral CD34+ cells, played a role in CD34+ differentiation into megakaryocytes and was released from mature megakaryocytes, suggesting the source of circulating BDNF as potentially megakaryocytic.

    Learning Objectives:

    • Upon completion, participant will be able to evaluate the expression of BDNF and its receptors in CD34+ derived megakaryocytes.
    • Upon completion, participant will be able to apperciate the role of BDNF in the differentiation and maturation of CD34+ derived megakaryocytes.
    • Upon completion, participant will be able to discuss how CD34+ derived megakaryocytes release BDNF and its precursor, proBDNF, during differentiation and maturation.