A microfluidic approach to study the effect of mechanical stress on erythrocytes in sickle cell disease

Author(s):Show less -

Iragorri, Maria Alejandra Lizarralde ^{[1, 2, 3]} ; El Hoss, Sara ^{[1, 2, 3]} ; Brousse, Valentine ^{[1, 2, 3, 4]} ; Lefevre, Sophie D. ^{[1, 2, 3]} ; Dussiot, Michael ^[5] ; Xu, Tieying ^[6] ; Ferreira, Alexander Rodrigo ^[7] ; Lamarre, Yann ^[7] ; Silva Pinto, Ana Cristina ^[7] ; Kashima, Simone ^[7] ; Lapoumeroulie, Claudine ^{[1, 3]} ; Covas, Dimas Tadeu ^{[8, 7]} ; Le Van Kim, Caroline ^{[1, 2, 3]} ; Colin, Yves ^{[1, 2, 3]} ; Elion, Jacques ^{[1, 2, 3]} ; Francais, Olivier ^[9] ; Le Pioufle, Bruno ^[6] ; El Nemer, Wassim ^{[1, 2, 3]}

Affiliation

^[1] Inst Natl Transfus Sanguine, F-75015 Paris - France

^[2] Univ Antilles, Univ La Reunion, Sorbonne Paris Cite, Biol Integree Globule Rouge, INSERM, Univ Paris Diderot, INTS, UMR S1134, 6 Rue Alexandre Cabanel, F-75015 Paris - France

^[3] Lab Excellence GR Ex, Paris - France

^[4] Hop Necker Enfants Malad, AP HP, Serv Pediat Gen, Ctr Reference Drepanocytose, Paris - France

^[5] Univ Paris 05, Univ Sorbonne Paris Cite, Lab Cellular & Mol Mech Hematol Disorders & Thera, INSERM, Lab Excellence GR Ex, CNRS, Inst Imagine, Paris - France

^[6] Univ Paris Saclay, ENS Paris Saclay, Inst dAlembert, CNRS, SATIE, Ile De France - France

^[7] Hemoctr Ribeirao Preto, Ctr Cell Based Therapy, Sao Paulo - Brazil

^[8] Univ Sao Paulo, Ribeirao Preto Med Sch, Ribeirao Preto, SP - Brazil

^[9] Univ Paris Est, ESYCOM EA2552, ESIEE Paris, Noisy Le Grand - France

• Document type: Journal article
• Source: LAB ON A CHIP; v. 18, n. 19, p. 2975-2984, OCT 7 2018.
• Web of Science Citations: 6

Abstract

The human red blood cell is a biconcave disc of 6-8 x 2 mu m that is highly elastic. This capacity to deform enables it to stretch while circulating through narrow capillaries to ensure its main function of gas exchange. Red cell shape and deformability are altered in membrane disorders because of defects in skeletal or membrane proteins affecting protein-protein interactions. Red cell properties are also altered in other pathologies such as sickle cell disease. Sickle cell disease is a genetic hereditary disorder caused by a single point mutation in the beta-globin gene generating sickle haemoglobin (HbS). Hypoxia drives HbS polymerisation that is responsible for red cell sickling and reduced deformability. The main clinical features of sickle cell disease are vaso-occlusive crises and haemolytic anaemia. Foetal haemoglobin (HbF) inhibits HbS polymerisation and positively impacts red cell survival in the circulation but the mechanism through which it exerts this action is not fully characterized. In this study, we designed a microfluidic biochip mimicking the dimensions of human capillaries to measure the impact of repeated mechanical stress on the survival of red cells at the single cell scale under controlled pressure. We show that mechanical stress is a critical parameter underlying intravascular haemolysis in sickle cell disease and that high intracellular levels of HbF protect against lysis. The biochip is a promising tool to address red cell deformability in pathological situations and to screen for molecules positively impacting this parameter in order to improve red cell survival in the circulation. (AU)

• FAPESP's process: 13/08135-2 - CTC - Center for Cell-Based Therapy
• Grantee: Dimas Tadeu Covas
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC