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Recent Advancements in Hematology: Knowledge, Methods and Dissemination, Part 1
Article

Doxorubicin Enhances Procoagulant Activity of Endothelial Cells after Exposure to Tumour Microparticles on Microfluidic Devices

Department of Biomedical Science, The University of Hull, Hull HU6 7RX, UK
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Hemato 2020, 1(1), 23-34; https://doi.org/10.3390/bloods1010006
Received: 11 June 2020 / Revised: 17 July 2020 / Accepted: 21 July 2020 / Published: 23 July 2020
The majority of cancer patients undergoing chemotherapy have a significantly increased risk of venous thromboembolism via a mechanism not yet fully elucidated but which most probably involves tumour microparticles (MP) combined with damaged/activated endothelium. Tumour cell lines (ES-2 and U87) were cultured as 3D spheroids and transferred to biochips connected through to a second chip precultured with an endothelial cell layer (human umbilical vein endothelial cells [HUVECs]). Media were introduced with and without doxorubicin (DOX) to the spheroids in parallel chips under constant flow conditions. Media samples collected pre- and post-flow through the biochip were analysed for tissue factor microparticles (TFMP) and procoagulant activity (PCA). HUVECs were also harvested and tested for PCA at a constant cell number. TFMP levels in media decreased after passing over HUVECs in both conditions over time and this was accompanied by a reduction in PCA (indicated by a slower coagulation time) of the media. The relationship between PCA and TFMP was correlated (r = −0.85) and consistent across experiments. Harvested HUVECs displayed increased PCA when exposed to tumour spheroid media containing TFMP, which was increased further after the addition of DOX, suggesting that the TFMP in the media had bound to HUVEC cell surfaces. The enhanced PCA of HUVECs associated with the DOX treatment was attributed to a loss of viability of these cells rather than additional MP binding. The data suggest that tumour MP interact with HUVECs through ligand-receptor binding. The model described is a robust and reproducible method to investigate cytotoxic agents on tumour spheroids and subsequent downstream interaction with endothelial cells. View Full-Text
Keywords: doxorubicin; microparticles; microfluidics; endothelium doxorubicin; microparticles; microfluidics; endothelium
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MDPI and ACS Style

Algarni, A.; Greenman, J.; Madden, L.A. Doxorubicin Enhances Procoagulant Activity of Endothelial Cells after Exposure to Tumour Microparticles on Microfluidic Devices. Hemato 2020, 1, 23-34. https://doi.org/10.3390/bloods1010006

AMA Style

Algarni A, Greenman J, Madden LA. Doxorubicin Enhances Procoagulant Activity of Endothelial Cells after Exposure to Tumour Microparticles on Microfluidic Devices. Hemato. 2020; 1(1):23-34. https://doi.org/10.3390/bloods1010006

Chicago/Turabian Style

Algarni, Abdulrahman, John Greenman, and Leigh A. Madden 2020. "Doxorubicin Enhances Procoagulant Activity of Endothelial Cells after Exposure to Tumour Microparticles on Microfluidic Devices" Hemato 1, no. 1: 23-34. https://doi.org/10.3390/bloods1010006

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