Biophysical and rheological biomarkers of red blood cell physiology and pathophysiology

Abstract

Purpose of review This review summarizes the significant biophysical and rheological aspects of red blood cell physiology and pathophysiology in relation to recent advances in microfluidic biomarker assays and emerging targeted or curative intent therapies. Recent findings Alterations in red cell biophysical properties and blood rheology have been associated with numerous hematologic and circulatory disorders. Recent advances in biomarker assays enable effective assessment of these biophysical and rheological properties in normoxia or physiological hypoxia in a clinically meaningful way. There are emerging targeted or curative therapies that aim to improve red cell pathophysiology, especially in the context of inherited hemoglobin disorders, such as sickle cell disease. Summary Red cell pathophysiology can be therapeutically targeted and the improvements in membrane and cellular biophysics and blood rheology can now be feasibly assessed via new microfluidic biomarker assays. Recent advances provide a new hope and novel treatment options for major red cell ailments, including inherited hemoglobin disorders, membrane disorders, and other pathologies of the red cell, such as malaria.

A retrospective case study of successful translational research: Gazelle Hb variant point-of-care diagnostic device for sickle cell disease

“…SCD emerges when such mutations are inherited from both parents, homozygously (Hb SS) or together with another β-globin gene mutation, such as hemoglobin C (Hb SC) or β-thalassemia (compound heterozygous, Hb Sβthal+/0). In SCD, abnormal polymerization of deoxygenated sickle hemoglobin results in stiff red blood cells (RBCs), alters shape, and triggers inflammation and endothelial cell activation 13 . These RBCs are stiff and adhesive in the small blood vessels, particularly where the oxygen tension is relatively low, such as the kidney or spleen 13 .…”

“…In SCD, abnormal polymerization of deoxygenated sickle hemoglobin results in stiff red blood cells (RBCs), alters shape, and triggers inflammation and endothelial cell activation 13 . These RBCs are stiff and adhesive in the small blood vessels, particularly where the oxygen tension is relatively low, such as the kidney or spleen 13 . These abnormalities result in vascular occlusion and can stop blood flow to vital organs 14 .…”

Cell and Gene Therapy for Anemia: Hematopoietic Stem Cells and Gene Editing

“…SCD features a vicious circle between inflammation and abnormal RBC rheology [38], which modulates clinical severity in patients. Chronic inflammation leads to organ dysfunction in SCD patients.…”

“…In an SCD patient with MC, the expression of the apoptotic regulator Fas was significantly higher in the recipient erythroblasts and RBCs than in the donor erythroblasts and RBCs, suggesting that SCD "ineffective" erythroid cells undergo apoptosis, whereas donor cells have a survival advantage. Stable donor chimerism greater than 25% is associated with the resolution of SCD-related symptoms [36][37][38].…”

Proteomic Analysis of the Role of the Adenylyl Cyclase–cAMP Pathway in Red Blood Cell Mechanical Responses

“…Given that the synthesis of novel proteins does not occur, the vital cellular functions would be maintained by post-translational modifications of the existing proteins via phosphorylation. Phosphorylation contributes to the pathogenesis of sickle cell disease [ 19 , 20 , 21 ] or malaria [ 22 , 23 ] and regulates redox stress [ 24 ] or the interactions between cytoskeletal and membrane proteins [ 25 , 26 , 27 ].…”