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Ferrata Storti Foundation
Haematologica 2019 Volume 104(3):428-434
Endothelialized flow models for blood transfusion research
Monica S.Y. Ng,1,2 Jacky Y. Suen,1 John-Paul Tung1,2 and John F. Fraser1
1Critical Care Research Group, Faculty of Medicine, University of Queensland, Brisbane and 2Research and Development, Australian Red Cross Blood Service, Brisbane, Australia
Introduction
Recent advances in cell culture and microfabrication technologies have enabled the development of perfusable endothelialized channels in vitro. To date, these techniques have primarily been applied to tissue engineering research. However, this set-up provides the unique opportunity to simulate blood product transfusion in a cost-effective, robust and reproducible manner – incorporating blood, endothelial and flow components in one unit. This Perspective describes the value of vascular models in transfusion research and discusses key decision points in the design process.
What happens to blood after transfusion?
On transfusion, blood products interact with blood cells and plasma compo- nents to alter platelet activation, leukocyte function and red blood cell (RBC) oxy- gen-carrying capacity. The pro-/anti-inflammatory balance hinges on whether neutrophil or macrophage responses dominate after blood product transfusion.1-3 These responses are dependent on the activation state of recipient neutrophils and macrophages which, in turn, is influenced by cytokines in the local microenviron- ment. RBCs and platelets modify immune system function by activating comple- ment, releasing cytokines and participating in receptor-ligand interactions.4
Blood products and recipient blood are encased by endothelium in blood ves- sels, one of the largest organs in the body with a surface area of 350-1000 m2.5 The endothelium conveys blood to tissues, provides a surface that prevents improper clotting and cellular activation, acts as a selective barrier to macromolecule extravasation and regulates microvascular blood flow.6 Activated endothelium participates in inflammation by releasing chemotactic molecules (e.g., interleukin- 8 and monocyte chemoattractant protein-1), generating reactive oxygen species and expressing adhesion molecules (CD62, CD106, CD54, CD31) to attract leuko- cytes and facilitate leukocyte transmigration.7,8 Furthermore, activated endotheli- um also enhances thrombosis by elaborating procoagulant surface molecules (von Willebrand factor, tissue factor) and microparticles.8 Endothelial dysfunction has been implicated in transfusion-related acute lung injury, sepsis and multiple organ dysfunction.8,9
The mixture of blood product and recipient blood is constantly mixed and pro- pelled by the cardiac cycle – maximizing cellular interactions and minimizing inappropriate endothelial adhesion.10 After leaving the heart, blood flows through arteries to reach capillaries in the tissues and then veins before returning to the heart. The three types of blood vessels differ in structure, diameter, flow patterns and shear stress.10 In arteries and veins, RBCs and leukocytes flow in the center of the flow stream and platelets are distributed to the periphery of the stream.11 RBCs exhibit a parabolic velocity profile with shear-dependent rotation which continuously mixes the blood components. The configuration of cells in the flow stream can be modified by RBC plasticity, shear rate and fluid viscosity.12,13 In the microvasculature, cells travel in single file with uniform distribution of platelets, RBCs and leukocytes in the flow stream.
Additionally, blood flow exerts shear stress on endothelium thereby altering endothelial gene expression, apoptosis, migration, permeability and alignment.6,14 Endothelial cells cultured under flow conditions demonstrate enhanced barrier function in conjunction with minimal adhesion molecule activation.15,16 Physiological shear stress is protective against inappropriate endothelial cytokine release compared to low shear stress.9 Additionally, flow patterns (e.g. continuous versus pulsatile) influence endothelial adhesion protein expression, structure and
Correspondence:
MONICA S.Y. NG
monica.ng91@gmail.com
Received: October 31, 2018. Accepted: January 15, 2019. Pre-published: February 14, 2019.
doi:10.3324/haematol.2018.205203
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/103/4/428
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