RT Journal Article
SR Electronic
T1 In-vitro modeling of micro-emboli and their effect on microvascular circulation and endothelium mechanics
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 3572
DO 10.1183/13993003.congress-2020.3572
VO 56
IS suppl 64
A1 Lucilla Piccari
A1 Andrea Malandrino
A1 Diego A Rodríguez
A1 James Sharpe
YR 2020
UL http://erj.ersjournals.com/content/56/suppl_64/3572.abstract
AB Aims & Objectives: microembolization in microvasculature is observed in diseases like embolic stroke and acute pulmonary embolism (APE). In the lung, micro-emboli lead to increased vascular resistance and heart failure. The objective of our study was to model embolization in microvasculature on a chip and study the biomechanical response.Methods: we used two cellular types, the established Human Umbilical Vein Endothelial Cells (HUVEC) and lung-specific Human Pulmonary Artery Endothelial Cells (HPAEC) to create self-organized microvasculature in microfluidics chips. We diluted carboxylated micro-beads (~5 mm) perfusing them with a controlled pressure head, visualizing flow in real-time with nano-tracers of distinct fluorescence. We perfused them sequentially, before and after embolization, during a 3D confocal image acquisition, while acquiring high-speed time-lapses and using Particle Image Velocimetry (PIV) to quantify fluid velocity of the nano-tracers. We also use the PIV algorithm on labeled fibrin gel to measure extracellular matrix (ECM) mechanical deformations.Results: despite some variability, in vitro microembolization decreases up to 75% the perfused area, with flow redirection and preferential paths after micro-embolization. Preliminary results show fibrin deformations in poorly perfused endothelia. These observations may suggest a rapid mechanical adaptation to micro-obstructions and might help understand the physiopathology of APE and other embolic disorders. Our in vitro microembolization model paves the way to integrate the study of endothelium mechanics and fluid perfusion disturbances in 3D using a realistic self-organized microvasculature.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3572.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).