Microfluidic methods to advance mechanistic understanding and translational research in sickle cell disease

• Type of Material: Article
• Authors: Melissa Azul, Mayo Clinic; Eudorah F. Vital, Emory University; Wilbur Lam, Emory University; David K. Wood, University of Minnesota; Joan D. Beckman, University of Minnesota
• Language: English
• Date: 2022-06-09
• Publisher: ELSEVIER SCIENCE INC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2022 Elsevier Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.trsl.2022.03.010
• Title of Journal or Parent Work: TRANSLATIONAL RESEARCH
• Volume: 246
• Start Page: 1
• End Page: 14
• Grant/Funding Information: Portions of this work were conducted in the Minnesota Nano Center, which is supported by the National Science Foundation through the National Nanotechnology Coordinated Infrastructure (NNCI) under Award Number ECCS-2025124. E.F.V. is supported by F31HL158223. W.A.L. is supported by R35HL145000. W.A.L. and D.K.W. are supported by R01HL140589. D.K.W is supported by HL132906. J.D.B. is supported in part by Institutional Research Grant #129819-IRG-16–189-58-IRG-114 from the American Cancer Society, OT2 HL15275801, an American Society of Hematology Restart Award and American Heart Association Career Development Award.
• Keywords: DEFORMABILITY; PAINFUL CRISES; HYDROXYUREA; Medicine, Research & Experimental; Research & Experimental Medicine; MODEL; Medicine, General & Internal; ADHESION; FETAL-HEMOGLOBIN; GENE-THERAPY; Medical Laboratory Technology; ERYTHROCYTES; BLOOD RHEOLOGY; ANEMIA; Life Sciences & Biomedicine; Science & Technology; General & Internal Medicine
• Research Categories: Biology, Anatomy; Biology, Genetics

Abstract

Sickle cell disease (SCD) is caused by a single point mutation in the β-globin gene of hemoglobin, which produces an altered sickle hemoglobin (HbS). The ability of HbS to polymerize under deoxygenated conditions gives rise to chronic hemolysis, oxidative stress, inflammation, and vaso-occlusion. Herein, we review recent findings using microfluidic technologies that have elucidated mechanisms of oxygen-dependent and -independent induction of HbS polymerization and how these mechanisms elicit the biophysical and inflammatory consequences in SCD pathophysiology. We also discuss how validation and use of microfluidics in SCD provides the opportunity to advance development of numerous therapeutic strategies, including curative gene therapies.