A microengineered model of RBC transfusion-induced pulmonary vascular injury

Abstract Red blood cell (RBC) transfusion poses significant risks to critically ill patients by increasing their susceptibility to acute respiratory distress syndrome. While the underlying mechanisms of this life-threatening syndrome remain elusive, studies suggest that RBC-induced microvascular inj...

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Autores principales:	Jeongyun Seo, David Conegliano, Megan Farrell, Minseon Cho, Xueting Ding, Thomas Seykora, Danielle Qing, Nilam S. Mangalmurti, Dongeun Huh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/daaf2e1d4f6a44859fede5e2e563f6d3
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spelling	oai:doaj.org-article:daaf2e1d4f6a44859fede5e2e563f6d32021-12-02T11:52:57ZA microengineered model of RBC transfusion-induced pulmonary vascular injury10.1038/s41598-017-03597-w2045-2322https://doaj.org/article/daaf2e1d4f6a44859fede5e2e563f6d32017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03597-whttps://doaj.org/toc/2045-2322Abstract Red blood cell (RBC) transfusion poses significant risks to critically ill patients by increasing their susceptibility to acute respiratory distress syndrome. While the underlying mechanisms of this life-threatening syndrome remain elusive, studies suggest that RBC-induced microvascular injury in the distal lung plays a central role in the development of lung injury following blood transfusion. Here we present a novel microengineering strategy to model and investigate this key disease process. Specifically, we created a microdevice for culturing primary human lung endothelial cells under physiological flow conditions to recapitulate the morphology and hemodynamic environment of the pulmonary microvascular endothelium in vivo. Perfusion of the microengineered vessel with human RBCs resulted in abnormal cytoskeletal rearrangement and release of intracellular molecules associated with regulated necrotic cell death, replicating the characteristics of acute endothelial injury in transfused lungs in vivo. Our data also revealed the significant effect of hemodynamic shear stress on RBC-induced microvascular injury. Furthermore, we integrated the microfluidic endothelium with a computer-controlled mechanical stretching system to show that breathing-induced physiological deformation of the pulmonary microvasculature may exacerbate vascular injury during RBC transfusion. Our biomimetic microsystem provides an enabling platform to mechanistically study transfusion-associated pulmonary vascular complications in susceptible patient populations.Jeongyun SeoDavid ConeglianoMegan FarrellMinseon ChoXueting DingThomas SeykoraDanielle QingNilam S. MangalmurtiDongeun HuhNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jeongyun Seo David Conegliano Megan Farrell Minseon Cho Xueting Ding Thomas Seykora Danielle Qing Nilam S. Mangalmurti Dongeun Huh A microengineered model of RBC transfusion-induced pulmonary vascular injury
description	Abstract Red blood cell (RBC) transfusion poses significant risks to critically ill patients by increasing their susceptibility to acute respiratory distress syndrome. While the underlying mechanisms of this life-threatening syndrome remain elusive, studies suggest that RBC-induced microvascular injury in the distal lung plays a central role in the development of lung injury following blood transfusion. Here we present a novel microengineering strategy to model and investigate this key disease process. Specifically, we created a microdevice for culturing primary human lung endothelial cells under physiological flow conditions to recapitulate the morphology and hemodynamic environment of the pulmonary microvascular endothelium in vivo. Perfusion of the microengineered vessel with human RBCs resulted in abnormal cytoskeletal rearrangement and release of intracellular molecules associated with regulated necrotic cell death, replicating the characteristics of acute endothelial injury in transfused lungs in vivo. Our data also revealed the significant effect of hemodynamic shear stress on RBC-induced microvascular injury. Furthermore, we integrated the microfluidic endothelium with a computer-controlled mechanical stretching system to show that breathing-induced physiological deformation of the pulmonary microvasculature may exacerbate vascular injury during RBC transfusion. Our biomimetic microsystem provides an enabling platform to mechanistically study transfusion-associated pulmonary vascular complications in susceptible patient populations.
format	article
author	Jeongyun Seo David Conegliano Megan Farrell Minseon Cho Xueting Ding Thomas Seykora Danielle Qing Nilam S. Mangalmurti Dongeun Huh
author_facet	Jeongyun Seo David Conegliano Megan Farrell Minseon Cho Xueting Ding Thomas Seykora Danielle Qing Nilam S. Mangalmurti Dongeun Huh
author_sort	Jeongyun Seo
title	A microengineered model of RBC transfusion-induced pulmonary vascular injury
title_short	A microengineered model of RBC transfusion-induced pulmonary vascular injury
title_full	A microengineered model of RBC transfusion-induced pulmonary vascular injury
title_fullStr	A microengineered model of RBC transfusion-induced pulmonary vascular injury
title_full_unstemmed	A microengineered model of RBC transfusion-induced pulmonary vascular injury
title_sort	microengineered model of rbc transfusion-induced pulmonary vascular injury
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/daaf2e1d4f6a44859fede5e2e563f6d3
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A microengineered model of RBC transfusion-induced pulmonary vascular injury

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