title: Platelet bioreactor-on-a-chip.
abstract: Platelet 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.
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Thon
authors.forename: Linas
authors.initials: L
authors.lastname: Mazutis
authors.forename: Stephen
authors.initials: S
authors.lastname: Wu
authors.forename: Joanna L
authors.initials: JL
authors.lastname: Sylman
authors.forename: Allen
authors.initials: A
authors.lastname: Ehrlicher
authors.forename: Kellie R
authors.initials: KR
authors.lastname: Machlus
authors.forename: Qiang
authors.initials: Q
authors.lastname: Feng
authors.forename: Shijiang
authors.initials: S
authors.lastname: Lu
authors.forename: Robert
authors.initials: R
authors.lastname: Lanza
authors.forename: Keith B
authors.initials: KB
authors.lastname: Neeves
authors.forename: David A
authors.initials: DA
authors.lastname: Weitz
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Italiano
mesh_terms: D000818:Animals; D040761:Biomimetic Materials; D019149:Bioreactors; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology; D004867:Equipment Design; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000502:physiology; D051379:Mice; D046210:Microfluidic Analytical Techniques; D008954:Models, Biological; D017713:Platelet Transfusion; D034061:Thrombopoiesis