Leading the way in experimental and clinical research in hematology

Platelet bioreactor-on-a-chip

  1. Jonathan N. Thon1,*,
  2. Linas Mazutis2,
  3. Stephen Wu1,
  4. Joanna L. Sylman3,
  5. Allen Ehrlicher4,
  6. Kellie R. Machlus5,
  7. Qiang Feng6,
  8. Shijiang Lu6,
  9. Robert Lanza6,
  10. Keith B. Neeves7,
  11. David A. Weitz2, and
  12. Joseph E. Italiano Jr.1
  1. 1 Department of Medicine, Brigham and Women's Hospital, Boston, MA, United States;
  2. 2 School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United States;
  3. 3 Department of Chemical and Biological Engineering, Colorado School of Mines, Golden, CO, United States;
  4. 4 Department of Bioengineering, McGill University, Montreal, QC, Canada;
  5. 5 Department of Medicine, Harvard Medical School, Boston, MA, United States;
  6. 6 Advanced Cell Technologies, Advanced Cell Technologies, Marlborough, MA, United States;
  7. 7 Department of Pediatrics, University of Colorado, Denver, CO, United States
  1. * Corresponding author; email: drjthon{at}gmail.com

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.