Abstract 13354: Thrombopoiesis Processes in Bone Marrows Programmed by Cytokine Balances Visualized by in vivo Imaging
Blood platelets are generated in the bone marrow (BM) from their precursors, megakaryocytes (MK). Although we know that MKs produce platelets throughout life, precisely how platelets are produced in vivo remains uncertain, largely because of the rarity of MKs in the BM and the lack an adequate visualization technique. In the present study, we were able to visualize MK dynamics leading to platelet release in living animals at high resolution.
By visualizing living bone marrow in vivo, we observed that two modes (fragmentation and proplatelet formation) can be ongoing simultaneously in the same mouse. Cytokine balance determines how quickly and through what strategy platelets are produced by MKs.
Whereas proplatelet formation predominated in control mice, acute blood loss or platelet depletion through 5-fluorouracil administration induced a change to MK fragmentation. This change was facilitated by some humoral factors during the acute phase following platelet reduction, while thrombopoietin enhanced formation of elongated proplatelets during the chronic phase of recovery. These factors were identified by combination of in vitro screening systems and in vivo MK visualization analysis. Factor serum levels were reduced independently of the thrombopoietin level in human subjects with low platelet counts. It thus appears the cytokine balance dynamically regulates the mode of thrombopoiesis and the cellular programming of MKs. Thus, these novel factor may be a novel therapeutic target in thrombocytopenic situations, especially when associated with acute loss of platelets or when platelet transfusion is limited or unsuccessful.
- © 2013 by American Heart Association, Inc.