Abstract:

Jonathan N. Thon1,2,3, Linas Mazutis3,4,5, Stephen Wu1, Joanna L. Sylman6, Allen Ehrlicher4,7, Kellie R. Machlus1,2, Qiang Feng8, Shijiang Lu8, Robert Lanza8, Keith B. Neeves6,9, David A. Weitz4, and Joseph E. Italiano Jr1,2,3,101Department of Medicine, Brigham and Women’s Hospital, Boston, MA; 2Harvard Medical School, Boston, MA; 3Platelet BioGenesis, Chestnut Hill, MA; 4School of Engineering and Applied Sciences, Harvard University, Cambridge, MA; 5Institute of Biotechnology, Vilnius University, Vilnius, Lithuania; 6Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, CO; 7Department of Bioengineering, McGill University, Montreal, Canada; 8Advanced Cell Technologies, Marlborough, MA; 9Department of Pediatrics, University of Colorado, Denver, Aurora, CO; and 10Department of Surgery, Vascular Biology Program, Boston Children’s Hospital, Boston, MAKey PointsWe have developed a biomimetic microfluidic platelet bioreactor that recapitulates bone marrow and blood vessel microenvironments.Application of shear stress in this bioreactor triggers physiological proplatelet production, and platelet release.AbstractPlatelet transfusions total >2.17 million apheresis-equivalent units per year in the United States and are derived entirely from human donors, despite clinically significant immunogenicity, associated risk of sepsis, and inventory shortages due to high demand and 5-day shelf life. To take advantage of known physiological drivers of thrombopoiesis, we have developed a microfluidic human platelet bioreactor that recapitulates bone marrow stiffness, extracellular matrix composition, micro-channel size, hemodynamic vascular shear stress, and endothelial cell contacts, and it supports high-resolution live-cell microscopy and quantification of platelet production. Physiological shear stresses triggered proplatelet initiation, reproduced ex vivo bone marrow proplatelet production, and generated functional platelets. Modeling human bone marrow composition and hemodynamics in vitro obviates risks associated with platelet procurement and storage to help meet growing transfusion needs.Submitted May 9, 2014.Accepted July 8, 2014.© 2014 by The American Society of Hematology

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