Platelet bioreactor-on-a-chip

被引:158
作者
Thon, Jonathan N. [1 ,2 ,3 ]
Mazutis, Linas [3 ,4 ,5 ]
Wu, Stephen [1 ]
Sylman, Joanna L. [6 ]
Ehrlicher, Allen [4 ,7 ]
Machlus, Kellie R. [1 ,2 ]
Feng, Qiang [8 ]
Lu, Shijiang [8 ]
Lanza, Robert [8 ]
Neeves, Keith B. [6 ,9 ]
Weitz, David A. [4 ]
Italiano, Joseph E., Jr. [1 ,2 ,3 ,10 ]
机构
[1] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA USA
[3] Platelet BioGenesis, Chestnut Hill, MA USA
[4] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA
[5] Vilnius State Univ, Inst Biotechnol, Vilnius, Lithuania
[6] Colorado Sch Mines, Dept Chem & Biol Engn, Golden, CO 80401 USA
[7] McGill Univ, Dept Bioengn, Montreal, PQ, Canada
[8] Adv Cell Technol, Marlborough, MA USA
[9] Univ Colorado, Dept Pediat, Denver, CO 80202 USA
[10] Boston Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA USA
基金
美国国家卫生研究院;
关键词
EMBRYONIC STEM-CELLS; IN-VITRO; FUNCTIONAL PLATELETS; HUMAN MEGAKARYOCYTES; GENERATION; RELEASE; PROGENITORS; INHIBITION; INVITRO; SYSTEM;
D O I
10.1182/blood-2014-05-574913
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1857 / 1867
页数:11
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