Thon Jonathan N, Mazutis Linas, Wu Stephen, Sylman Joanna L, Ehrlicher Allen, Machlus Kellie R, Feng Qiang, Lu Shijiang, Lanza Robert, Neeves Keith B, Weitz David A, Italiano Joseph E
Blood. 2014 Sep 18;124(12):1857-67. doi: 10.1182/blood-2014-05-574913.
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.
在美国,每年血小板输注总量超过217万个单采等效单位,且完全来自人类供体,尽管存在临床上显著的免疫原性、败血症相关风险以及由于高需求和5天保质期导致的库存短缺。为了利用已知的血小板生成生理驱动因素,我们开发了一种微流控人血小板生物反应器,该反应器概括了骨髓硬度、细胞外基质组成、微通道大小、血液动力学血管剪切应力和内皮细胞接触,并且支持高分辨率活细胞显微镜检查和血小板生成定量。生理剪切应力触发前血小板起始,在体外重现骨髓前血小板生成,并产生功能性血小板。在体外模拟人类骨髓组成和血液动力学可消除与血小板采集和储存相关的风险,以帮助满足不断增长的输血需求。