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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

In vitro microfluidic model for the study of vaso-occlusive processes

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Autor(es):
Dominical, Venina M. [1] ; Vital, Daiana M. [1] ; O'Dowd, Frank [2] ; Saad, Sara T. O. [1] ; Costa, Fernando F. [1] ; Conran, Nicola [1]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Estadual Campinas, Sch Med, Hematol & Hemotherapy Ctr, INCT Sangue, Sao Paulo - Brazil
[2] Cellix Ltd, Dublin - Ireland
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: Experimental Hematology; v. 43, n. 3, p. 223-228, MAR 2015.
Citações Web of Science: 9
Resumo

Vaso-occlusion, responsible for much of the morbidity of sickle-cell disease, is a complex multicellular process, apparently triggered by leukocyte adhesion to the vessel wall. The microcirculation represents a major site of leukocyte-endothelial interactions and vasoocclusive processes. We have developed a biochip with subdividing interconnecting microchannels that decrease in size (40 mu m to 10 mu m in width), for use in conjunction with a precise microfluidic device, to mimic cell flow and adhesion through channels of sizes that approach those of the microcirculation. The biochips were utilized to observe the dynamics of the passage of neutrophils and red blood cells, isolated from healthy and sickle-cell anemia (SCA) individuals, through laminin or endothelial adhesion molecule-coated microchannels at physiologically relevant rates of flow and shear stress. Obstruction of E-selectin/intercellular adhesion molecule 1 coated biochip microchannels by SCA neutrophils was significantly greater than that observed for healthy neutrophils, particularly in the microchannels of 40-15 mu m in width. Whereas SCA red blood cells alone did not significantly adhere to, or obstruct, microchannels, mixed suspensions of SCA neutrophils and red blood cells significantly adhered to and obstructed laminin-coated channels. Results from this in vitro microfluidic model support a primary role for leukocytes in the initiation of SCA occlusive processes in the microcirculation. This assay represents an easy-to-use and reproducible in vitro technique for understanding molecular mechanisms and cellular interactions occurring in subdividing microchannels of widths approaching those observed in the microvasculature. The assay could hold potential for testing drugs developed to inhibit occlusive mechanisms such as those observed in SCA and thrombotic diseases. Copyright (C) 2015 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. (AU)

Processo FAPESP: 10/17320-0 - Adesão de células hematopoiéticas: mecanismos moleculares e inflamatórios
Beneficiário:Nicola Amanda Conran Zorzetto
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 10/18386-4 - Avaliação de interações heterotípicas de neutrófilos em condições inflamatórias
Beneficiário:Venina Marcela Dominical
Linha de fomento: Bolsas no Brasil - Doutorado