Journal of Biotechnology & Biomaterials
Open Access

Abstract

We established an in vitro model for human cord blood CD34+ progenitors for megakaryocytic diff erentiation into pro-platelets, shedding of immature/mature platelets and miropartiles (MPs), and for analysis of in vitro platelet senescence in human haemapheretic platelet preparations to analyze platelets, shedded microparticles and surrounding autologous plasma over 5 days with multi-omics platform. Our work provided evidence that ABCA1 is a central regulator for platelet shedding in megakaryocytes and also controls cargo packing of platelet granules during platelet formation, whereby treatment of megakaryocytes with HDL3/apo A-I induces extensive podia formation and platelet shedding. Comparison of mass spectrometric lipid class data of diff erentiating megakaryocytes, from platelets and plasma undergoing senescence, as well as from MPs, revealed that senescent platelets are enriched in cholesteryl esters (CEs), especially CE 18:2, originating from plasmatic lecethin-cholesterol-acyltransferase (LCAT) activity, indicating that platelets, in contrast to megakaryocytes, store plama lipid and lipoprotein in their unique open canalicular system (OCS), comprising up to 30 % of the platelet volume (R�¼bsaamen et al.: Transfusion 50: 1665-76, 2010). Ceramide (Cer) levels in diff erentiating megakaryocytes, in senescent platelets and in shedded microparticles (MPs) increased, suggesting an involvement of a shift of the equilibrium of the â��Cer-S1P rheostatâ�� from S1P towards Cer induced G-protein coupled signaling. Compared to megakaryocytes, platelets and miropartikles (MPs) are enriched in nucleic acid binding proteins, which could be involved in binding and regulation miRNA bound to MPs.

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