3D Cell-Culture Models for the Assessment of Anticoagulant and Anti-Inflammatory Properties of Endothelial Cells.

Sfriso, Riccardo; Rieben, Robert (2020). 3D Cell-Culture Models for the Assessment of Anticoagulant and Anti-Inflammatory Properties of Endothelial Cells. In: Xenotransplantation. Methods in Molecular Biology: Vol. 2110 (pp. 83-97). Springer 10.1007/978-1-0716-0255-3_6

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Endothelial cells (EC) play a crucial role in the pathophysiology of cardiovascular diseases, ischemia/reperfusion injury, and graft rejection in (xeno-)transplantation. In such nonphysiological conditions, EC are known to lose their quiescent phenotype and switch into an actively pro-inflammatory, procoagulant, and anti-fibrinolytic state. This case happens essentially because the endothelial glycocalyx-a layer of proteoglycans and glycoproteins covering the luminal surface of the endothelium-is shed. Heparan sulfate, one of the main components of the endothelial glycocalyx, contributes to its negative charge. In addition, many plasma proteins such as antithrombin III, superoxide dismutase, C1 inhibitor, and growth factors and cytokines bind to heparan sulfate and by this scenario contribute to the establishment of an anticoagulant and anti-inflammatory endothelial surface. Shedding of the glycocalyx results in a loss of plasma proteins from the endothelial surface, and this phenomenon causes the switch in phenotype. Particularly in xenotransplantation, both hyperacute and acute vascular rejection are characterized by coagulation dysregulation, a situation in which EC are the main players.Since many years, EC have been used in vitro in 2D flatbed cell culture models, with or without the application of shear stress. Such models have also been used to assess the effect of human transgenes on complement- and coagulation-mediated damage of porcine EC in the context of xenotransplantation. The methods described in this chapter include the analysis of endothelial cell-blood interactions without the necessity of using anticoagulants as the increased EC surface-to-volume ratio allows for natural anticoagulation of blood. Furthermore, this chapter contains the description of a novel microfluidic in vitro model carrying important features of small blood vessels, such as a 3D round-section geometry, shear stress, and pulsatile flow-all this in a closed circuit, recirculating system aiming at reproducing closely the in vivo situation in small vessels.

Item Type:

Book Section (Book Chapter)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Herz und Gefässe
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Sfriso, Riccardo and Rieben, Robert

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1940-6029

ISBN:

978-1-0716-0255-3

Series:

Methods in Molecular Biology

Publisher:

Springer

Language:

English

Submitter:

Marla Rittiner

Date Deposited:

17 Aug 2020 18:04

Last Modified:

17 Aug 2020 18:04

Publisher DOI:

10.1007/978-1-0716-0255-3_6

PubMed ID:

32002903

Uncontrolled Keywords:

3D cell culture Coagulation Complement Endothelial cells Genetic modifications Microcarrier beads Microfluidics Vascular biology Xenotransplantation

URI:

https://boris.unibe.ch/id/eprint/145963

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