A Microfluidics-Based Screening Tool to Assess the Impact of Blood Plasma Factors on Microvascular Integrity

Abidemi Junaid; Vincent van Duinen; Wendy Stam; Sophie Dólleman; Wei Yang; Yolanda de Rijke; Hendrik Endeman; Cees van Kooten; Alireza Mashaghi; Hetty de Boer; Janine van Gils; Thomas Hankemeier; Anton Jan van Zonneveld

doi:10.1002/adbi.202100954

A Microfluidics-Based Screening Tool to Assess the Impact of Blood Plasma Factors on Microvascular Integrity

Abidemi Junaid, Vincent van Duinen, Wendy Stam, Sophie Dólleman, Wei Yang, Yolanda de Rijke, Hendrik Endeman, Cees van Kooten, Alireza Mashaghi, Hetty de Boer, Janine van Gils, Thomas Hankemeier, Anton Jan van Zonneveld^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

This study provides a method to assess the impact of circulating plasma factors on microvascular integrity by using a recently developed microvessel-on-a-chip platform featuring the human endothelium that is partly surrounded by the extracellular matrix. The system is high-throughput, which allows parallel analysis of organ-level microvessel pathophysiology, including vascular leakage. Ethylenediaminetetraacetic acid plasma samples are mixed with inhibitors for recalcification of the plasma samples to avoid activation of the coagulation- or complement system. Moreover, the assay is validated by spiking vascular endothelial growth factor, histamine, or tumor necrosis factor alpha to recalcified plasma and confirms their modulation of microvessel barrier function at physiologically relevant concentrations. Finally, this study shows that perfusing the microvessels with recalcified plasma samples of coronavirus disease-2019 patients, with a confirmed proinflammatory profile, results in markedly increased leakage of the microvessels. The assay provides opportunities for diagnostic screening of inflammatory or endothelial disrupting plasma factors associated with endothelial dysfunction.

Original language	English
Article number	2100954
Journal	Advanced Biology
Volume	5
Issue number	11
DOIs	https://doi.org/10.1002/adbi.202100954
Publication status	Published - Nov 2021

Bibliographical note

Funding Information:
The authors like to thank John Lambris for providing compstatin in this study. This study was financially supported by the Dutch Heart Foundation CVON RECONNECT consortium and a ZonMW MKMD grant (114022501). Additional support was obtained from NWO-TTW (IMMUNMET, Grant No. 16249), TKI METABOCHIP project, ZonMW Health Holland HHOOCS grant Stabilise, Dutch Heart Foundation (Grant Nos. 2013T127 and 2018T095), and the LSH PPS grant METACOVID.

Funding Information:
The authors like to thank John Lambris for providing compstatin in this study. This study was financially supported by the Dutch Heart Foundation CVON RECONNECT consortium and a ZonMW MKMD grant (114022501). Additional support was obtained from NWO‐TTW (IMMUNMET, Grant No. 16249), TKI METABOCHIP project, ZonMW Health Holland HHOOCS grant Stabilise, Dutch Heart Foundation (Grant Nos. 2013T127 and 2018T095), and the LSH PPS grant METACOVID.

Publisher Copyright:
© 2021 The Authors. Advanced Biology published by Wiley-VCH GmbH

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A Microfluidics-Based Screening Tool to Assess the Impact of Blood Plasma Factors on Microvascular IntegrityFinal published version, 12.6 MBLicence: CC BY

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Junaid, A., van Duinen, V., Stam, W., Dólleman, S., Yang, W., de Rijke, Y., Endeman, H., van Kooten, C., Mashaghi, A., de Boer, H., van Gils, J., Hankemeier, T., & van Zonneveld, A. J. (2021). A Microfluidics-Based Screening Tool to Assess the Impact of Blood Plasma Factors on Microvascular Integrity. Advanced Biology, 5(11), Article 2100954. https://doi.org/10.1002/adbi.202100954

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title = "A Microfluidics-Based Screening Tool to Assess the Impact of Blood Plasma Factors on Microvascular Integrity",

abstract = "This study provides a method to assess the impact of circulating plasma factors on microvascular integrity by using a recently developed microvessel-on-a-chip platform featuring the human endothelium that is partly surrounded by the extracellular matrix. The system is high-throughput, which allows parallel analysis of organ-level microvessel pathophysiology, including vascular leakage. Ethylenediaminetetraacetic acid plasma samples are mixed with inhibitors for recalcification of the plasma samples to avoid activation of the coagulation- or complement system. Moreover, the assay is validated by spiking vascular endothelial growth factor, histamine, or tumor necrosis factor alpha to recalcified plasma and confirms their modulation of microvessel barrier function at physiologically relevant concentrations. Finally, this study shows that perfusing the microvessels with recalcified plasma samples of coronavirus disease-2019 patients, with a confirmed proinflammatory profile, results in markedly increased leakage of the microvessels. The assay provides opportunities for diagnostic screening of inflammatory or endothelial disrupting plasma factors associated with endothelial dysfunction.",

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note = "Funding Information: The authors like to thank John Lambris for providing compstatin in this study. This study was financially supported by the Dutch Heart Foundation CVON RECONNECT consortium and a ZonMW MKMD grant (114022501). Additional support was obtained from NWO-TTW (IMMUNMET, Grant No. 16249), TKI METABOCHIP project, ZonMW Health Holland HHOOCS grant Stabilise, Dutch Heart Foundation (Grant Nos. 2013T127 and 2018T095), and the LSH PPS grant METACOVID. Funding Information: The authors like to thank John Lambris for providing compstatin in this study. This study was financially supported by the Dutch Heart Foundation CVON RECONNECT consortium and a ZonMW MKMD grant (114022501). Additional support was obtained from NWO‐TTW (IMMUNMET, Grant No. 16249), TKI METABOCHIP project, ZonMW Health Holland HHOOCS grant Stabilise, Dutch Heart Foundation (Grant Nos. 2013T127 and 2018T095), and the LSH PPS grant METACOVID. Publisher Copyright: {\textcopyright} 2021 The Authors. Advanced Biology published by Wiley-VCH GmbH",

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AU - Dólleman, Sophie

AU - Yang, Wei

AU - de Rijke, Yolanda

AU - Endeman, Hendrik

AU - van Kooten, Cees

AU - Mashaghi, Alireza

AU - de Boer, Hetty

AU - van Gils, Janine

AU - Hankemeier, Thomas

AU - van Zonneveld, Anton Jan

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N2 - This study provides a method to assess the impact of circulating plasma factors on microvascular integrity by using a recently developed microvessel-on-a-chip platform featuring the human endothelium that is partly surrounded by the extracellular matrix. The system is high-throughput, which allows parallel analysis of organ-level microvessel pathophysiology, including vascular leakage. Ethylenediaminetetraacetic acid plasma samples are mixed with inhibitors for recalcification of the plasma samples to avoid activation of the coagulation- or complement system. Moreover, the assay is validated by spiking vascular endothelial growth factor, histamine, or tumor necrosis factor alpha to recalcified plasma and confirms their modulation of microvessel barrier function at physiologically relevant concentrations. Finally, this study shows that perfusing the microvessels with recalcified plasma samples of coronavirus disease-2019 patients, with a confirmed proinflammatory profile, results in markedly increased leakage of the microvessels. The assay provides opportunities for diagnostic screening of inflammatory or endothelial disrupting plasma factors associated with endothelial dysfunction.

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A Microfluidics-Based Screening Tool to Assess the Impact of Blood Plasma Factors on Microvascular Integrity

Abstract

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