Microvasculature-on-a-chip for the long-term study of endothelial barrier dysfunction and microvascular obstruction in disease.

Autor:	Qiu Y; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.; Winship Cancer Institute, Emory University, Atlanta, GA, USA.; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA., Ahn B; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.; Winship Cancer Institute, Emory University, Atlanta, GA, USA.; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA., Sakurai Y; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.; Winship Cancer Institute, Emory University, Atlanta, GA, USA.; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA., Hansen CE; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.; Winship Cancer Institute, Emory University, Atlanta, GA, USA.; Department of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, USA., Tran R; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.; Winship Cancer Institute, Emory University, Atlanta, GA, USA.; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA., Mimche PN; Department of Pathology, University of Utah, Salt Lake City, UT, United States., Mannino RG; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA.; Winship Cancer Institute, Emory University, Atlanta, GA, USA.; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA., Ciciliano JC; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA.; Winship Cancer Institute, Emory University, Atlanta, GA, USA.; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.; George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, Atlanta, GA, USA., Lamb TJ; Department of Pathology, University of Utah, Salt Lake City, UT, United States., Joiner CH; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA., Ofori-Acquah SF; Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Translational and International Hematology, Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.; School of Biomedical and Allied Health Sciences, College of Health Sciences, University of Ghana, Accra, Ghana., Lam WA; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, USA. wilbur.lam@emory.edu.; Department of Pediatrics, Division of Pediatric Hematology/Oncology, Aflac Cancer Center and Blood Disorders Center of Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, GA, USA. wilbur.lam@emory.edu.; Winship Cancer Institute, Emory University, Atlanta, GA, USA. wilbur.lam@emory.edu.; Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA. wilbur.lam@emory.edu.
Jazyk:	angličtina
Zdroj:	Nature biomedical engineering [Nat Biomed Eng] 2018; Vol. 2, pp. 453-463. Date of Electronic Publication: 2018 Apr 23.
DOI:	10.1038/s41551-018-0224-z
Abstrakt:	Alterations in the mechanical properties of erythrocytes occurring in inflammatory and hematologic disorders such as sickle cell disease (SCD) and malaria often lead to increased endothelial permeability, haemolysis, and microvascular obstruction. However, the associations among these pathological phenomena remain unknown. Here, we report a perfusable, endothelialized microvasculature-on-a-chip featuring an interpenetrating-polymer-network hydrogel that recapitulates the stiffness of blood-vessel intima, basement membrane self-deposition and self-healing endothelial barrier function for longer than 1 month. The microsystem enables the real-time visualization, with high spatiotemporal resolution, of microvascular obstruction and endothelial permeability under physiological flow conditions. We found how extracellular heme, a hemolytic byproduct, induces delayed but reversible endothelial permeability in a dose-dependent manner, and demonstrate that endothelial interactions with SCD or malaria-infected erythrocytes cause reversible microchannel occlusion and increased in situ endothelial permeability. The microvasculature-on-a-chip enables mechanistic insight into the endothelial barrier dysfunction associated with SCD, malaria and other inflammatory and haematological diseases. Competing Interests: Competing financial interests The authors declare no competing financial and non-financial interests.
Databáze:	MEDLINE
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