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

• 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
• Journal Title: TRANSLATIONAL RESEARCH
• Volume: Volume 246
• Publisher: ELSEVIER SCIENCE INC | 2022-06-09, Pages 1-14
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.trsl.2022.03.010
• Subjects: Biology, Genetics; Biology, Anatomy
• Keywords: Science & Technology; Life Sciences & Biomedicine; Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental; General & Internal Medicine; Research & Experimental Medicine; GENE-THERAPY; FETAL-HEMOGLOBIN; BLOOD RHEOLOGY; PAINFUL CRISES; ANEMIA; ADHESION; ERYTHROCYTES; DEFORMABILITY; HYDROXYUREA; MODEL

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.