A Three-Dimensional Microfluidic Device for Monitoring Cancer and Chemotherapy-Associated Platelet Activation.
A Three-Dimensional Microfluidic Device for Monitoring Cancer and Chemotherapy-Associated Platelet Activation.
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三维微流体装置，用于监测癌症和化学疗法相关的血小板激活。
DOI：
10.1021/acsomega.0c05572
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发表时间：
2021-02-02
期刊：
影响因子：
4.1
通讯作者：
Xia YL
中科院分区：
文献类型：
--
作者：
Hao Z;Lv H;Tan R;Yang X;Liu Y;Xia YL
在癌症患者中，尤其是化疗后，血小板活化和血栓形成的风险增加。我们之前的研究表明，化疗诱导的血小板活化主要是由于内皮细胞损伤。因此，简单的体外试验，如聚集试验，不适合用于预测血小板对不同化疗药物的反应性，因为其他因素，如肿瘤细胞、内皮细胞和血小板流速，也有助于癌症相关血栓的形成。因此，开发血小板检测系统，包括所有可能的风险参数，是必要的。在本研究中，我们描述了一种微工程微流控系统，该系统包含药物浓度发生器、癌细胞培养芯片和覆盖有融合内皮层的三维（3D）圆形微血管模型，并以稳定的流速灌注人血小板。阿霉素通过两个注射部位注射。通过计数、细胞骨架观察、内皮细胞或培养基中IACM1和ET-1水平评估内皮细胞损伤。将染色后的血小板灌注到人工血管中，观察血小板内皮细胞粘附情况。我们发现(i) MCF7细胞释放因子对内皮细胞和血小板都有细胞毒性作用。（ii）我们证实了阿霉素诱导的血小板活化是内皮细胞依赖性的。（iii）低剂量阿霉素（0 ~ 2.0 μM）诱导血小板活化，高剂量阿霉素（2.0 ~ 4.0 μM）诱导血小板死亡。我们的研究结果表明，血小板内皮细胞粘附可作为血小板活化的诊断标志物，为预测化疗前或化疗期间血小板反应性提供了一种简单快速的检测方法。
Platelet activation and the risk of thrombosis are increased in cancer patients, especially after chemotherapy. Our previous studies indicated that chemotherapy-induced platelet activation is largely due to endothelial cell damage. Thus, simple in vitro tests, such as aggregometry, are not desirable tests to predict platelet responsiveness to different chemotherapeutic agents because other contributory factors, such as tumor cells, endothelial cells, and the flow rate of platelets, also contribute to the formation of cancer-associated thrombosis. Therefore, developing a platelet detection system, which includes all possible risk parameters, is necessary. In the present study, we described a microengineered microfluidic system that contained a drug concentration generator, cancer cell culture chip, and three-dimensional (3D) circular microvascular model covered with a confluent endothelial layer and perfused with human platelets at a stable flow rate. Doxorubicin was injected through two injection sites. Endothelial cell injury was evaluated by counting, cell cytoskeleton observation, and the level of IACM1 and ET-1 in endothelial cells or a culture medium. Prestained platelets were perfused into the artificial blood vessel, and platelet-endothelial cell adhesion was measured. We found that (i) MCF7 cell-released factors had a cytotoxicity effect on both endothelial cells and platelets. (ii) We confirmed that doxorubicin-induced platelet activation was endothelial cell-dependent. (iii) A lower dosage of doxorubicin (0–2.0 μM) induced platelet activation, while a higher dosage of doxorubicin (2.0–4.0 μM) led to platelet death. Our findings indicated that platelet-endothelial cell adhesion could be used as a diagnostic marker of platelet activation, providing a simple and rapid detective way to predict platelet responsiveness before or during chemotherapy.
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影响因子：
10.4
作者：
Kim, E. -J.;Lim, K. -M.;Chung, J. -H.
通讯作者：
Chung, J. -H.
影响因子：
8.9
作者：
Baz, R;Li, L;Hussein, MA
通讯作者：
Hussein, MA
DOI：
10.1016/j.vascn.2006.02.014
发表时间：
2006-11-01
影响因子：
1.9
作者：
Li, Weiwei;Lam, Marilyn S.;Post, Joseph M.
通讯作者：
Post, Joseph M.
影响因子：
6.5
作者：
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通讯作者：
MCGREGOR, JL
影响因子：
6.2
作者：
Khorana, Alok A.;Dalal, Mehul;Connolly, Gregory C.
通讯作者：
Connolly, Gregory C.