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Platelet bioreactor-on-a-chip

Jonathan N. Thon, Linas Mazutis, Stephen Wu, Joanna L. Sylman, Allen Ehrlicher, Kellie R. Machlus, Qiang Feng, Shijiang Lu, Robert Lanza, Keith B. Neeves, David A. Weitz and Joseph E. Italiano Jr.

Key points

  • We 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.

Abstract

Platelet transfusions total >2.17 million apheresis-equivalent units/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 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 12, 2014.
  • Accepted July 8, 2014.