Shear enhances thrombopoiesis and formation of microparticles that induce megakaryocytic differentiation of stem cells
作者： Jinlin Jiang , Donna S. Woulfe , Eleftherios T. Papoutsakis
DOI: 10.1182/BLOOD-2014-01-547927
关键词:
摘要: In vivo visualization of thrombopoiesis suggests an important role for shear flow in platelet biogenesis. vitro, stress was shown to accelerate proplatelet formation from mature megakaryocytes (Mks). Yet, the biomechanical forces on Mk biology and biogenesis remains largely unexplored. this study, we investigated impact maturation platelet-like particles (PLPs), pro/preplatelets (PPTs), microparticles (MkMPs), furthermore, explored a physiological MkMPs. We found that accelerated DNA synthesis immature Mks exposure time– level–dependent manner. Both phosphatidylserine caspase-3 activation were enhanced by stress. Exposure dramatically increased generation PLPs/PPTs MkMPs up 10.8 47-fold, respectively. Caspase-3 inhibition reduced shear-induced PLP/PPT MkMP formation. PLPs generated under displayed improved functionality as assessed CD62P fibrinogen binding. Significantly, coculture with hematopoietic stem progenitor cells promoted cell differentiation synthesizing α- dense-granules, forming PPTs without exogenous thrombopoietin, thus identifying novel unexplored potential
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