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The OMEGA project:
Transfusion of platelet concentrates is the gold standard to treat patients with insufficient platelet counts (thrombocytopenia). Nevertheless, there are several risks associated with platelet transfusion, including alloimmunization, disease transmission, and infection during platelet collection and storage. Generation of in vitro cultured patient tailored platelets, overcomes these risks and has great potential to fulfil the ambition of developing novel transfusion products for personalized therapeutic treatment for patients at risk of bleeding. However the current state-of-the-art results in platelet-like particles of which characteristics merely approximate primary platelets and a disappointing low amount can be generated. To address and overcome these challenges the goal of OMEGA is to optimize in vitro megakaryopoiesis by implement the following work packages: WP1) Filling current knowledge gaps by comparing in vitro megakaryopoiesis with primary material (This vacancy), WP2) Improving final maturation by increasing lipid biogenesis, WP3) A systems biology integrative framework of megakaryopoiesis.Medical Priority Bleeding and Hemostasis:
The medical priority Bleeding and Hemostasis is an international frontrunner in applying state-of-the-art mass spectrometry-based proteomics in the area of transfusion medicine. We are a vibrant, international group of 35-40 colleagues (consisting of group leaders, postdocs, PhD students and technicians) that study the various aspects of hemostatic networks. Our department has academic affiliations with high-ranking universities in the Netherlands, such as Utrecht University and the University of Amsterdam. The departments research program benefits from excellent research facilities, which include the latest technology for biomolecular mass spectrometry, imaging and cell sorting.
Platelets are essential for hemostasis and play a key role in stopping bleeding. A severely decreased platelet count (generally <10-30×10^9 platelets/L), frequently observed in patients subjected to medical treatment (chemotherapy, radiation treatment or organ transplant surgery), is associated with life-threatening bleeding. To reduce this risk, transfusion of platelet concentrates is the treatment of choice. However, there are also risks involved in platelet transfusion itself. These include allo-immunization, transmission of blood borne diseases, and infection due to collection and storage methodology. These adverse outcomes could all be prevented if patient-catered platelets can be cultured in vitro. However, whereas in vivo a single megakaryocyte can produce 2000-3000 platelets within the bone marrow compartment (10^11 daily), in vitro megakaryocytes generate up to ~100 platelets per cell. Reproducing highly efficient platelet generation in vitro has proven a challenging task, which calls for elucidating the molecular and cellular mechanism underlying megakaryopoiesis. The overall aim of this project is to improve in vitro platelet biogenesis from stem cell-derived megakaryocytes (e.g. from induced pluripotent stem cells, iPSCs). Extensive characterization of in vivo megakaryopoiesis has not been performed. By comparing in vitro cultures with primary human material in this project you will delineate processes driven by factors that are missing in current culture protocols using omics approaches (e.g. mass spectrometry based proteomics and transcriptomics). Thereby we seek to gain a comprehensive insight into megakaryopoiesis to fill in the knowledge gaps that currently impede in vitro platelet production.
The mission of Sanquin is: “Together with the donor we ensure a better life for patients”. We are a knowledge-driven not-for-profit organization that supplies life-saving products and services, and focusses on blood transfusion medicine- and immunology- related research. This research is performed by a dedicated staff and is organized in four medical priorities, i.e.: Anemia, Bleeding and Hemostasis, Immunotherapy, and Immunity and inflammation. Sanquin’s research portfolio covers a broad spectrum ranging from basic to applied and clinical research and product- and process development. Sanquin provides a lively, internationally oriented, scientific environment with excellent facilities. We also organize weekly scientific meetings, journal clubs and work discussions to gain scientific input and to exchange knowledge.
Sanquin Blood Supply Foundation (Sanquin)
Plesmanlaan 125, 1066 CX, Amsterdam
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