Advances in Red Blood Cells Research (Closed)

A project collection of Cells (ISSN 2073-4409). This project collection belongs to the section "Cell Microenvironment".

Papers displayed on this page all arise from the same project. Editorial decisions were made independently of project staff and handled by the Editor-in-Chief or qualified Editorial Board members.

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Editors

Red Blood Cell Research Group, Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zürich, Switzerland
Interests: red blood cells; hypoxia; heterogeneity; redox signaling; anemia
Special Issues, Collections and Topics in MDPI journals

Project Overview

Dear Colleagues,

Red blood cells (RBCs) are the most abundant cells in mammals, including humans. They serve a well-known and well-described vital function. Furthermore, they are increasingly recognized as biomarkers for various pathophysiological conditions ranging from RBC-related diseases, such as hereditary and acquired anemias, to states and diseases that are not primarily linked to RBCs, such as inflammation, cancer, diabetes and cardiovascular disorders. Adaptation to environmental stressors such as hypoxia, hyper- and hypothermia, and practicing endurance and extreme sports also impacts the numbers and properties of red blood cells. Exploring the processes driving stem cells into erythroid differentiation and proliferation during erythropoiesis allows producing red blood cells of rare groups or those that may be used for transfusion for all patients. Today, “making one’s own red blood cells in a bioreaction” is a realistic future option; developing optimal methods for preserving red cells obtained from donors and storage in blood banks is of decisive importance for successful outcomes from blood transfusions.

We are pleased to invite you to contribute original articles, communications, and reviews covering the entire field of RBC research, including (but not limited to):

  • Erythropoiesis;
  • Membrane transport; 
  • Biophysical and biochemical RBC properties;
  • Collective phenomena;
  • The genesis, management and treatment of diseases;
  • The use of RBCs as drug carriers or biomarkers;
  • Adaptations to stress.

We look forward to receiving your contributions.

Prof. Dr. Anna Bogdanova
Prof. Dr. Lars Kaestner
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • red blood cells
  • metabolism
  • shape
  • adaptation
  • anemia
  • erythropoiesis
  • blood storage
  • senescence and clearance
  • signaling

Published Papers (15 papers)

2024

Jump to: 2023, 2022, 2021

6 pages, 194 KiB  
Editorial
Advances in Red Blood Cells Research
by Anna Bogdanova and Lars Kaestner
Cells 2024, 13(4), 359; https://doi.org/10.3390/cells13040359 - 18 Feb 2024
Viewed by 536
Abstract
This Editorial ‘Advances in Red Blood Cell Research’ is the preface for the special issue with the same title which files 14 contributions listed in Table 1 [...] Full article

2023

Jump to: 2024, 2022, 2021

12 pages, 929 KiB  
Systematic Review
Diagnostic Value and Prognostic Significance of Nucleated Red Blood Cells (NRBCs) in Selected Medical Conditions
by Katarzyna Pikora, Anna Krętowska-Grunwald, Maryna Krawczuk-Rybak and Małgorzata Sawicka-Żukowska
Cells 2023, 12(14), 1817; https://doi.org/10.3390/cells12141817 - 09 Jul 2023
Cited by 2 | Viewed by 6134
Abstract
Nucleated red blood cells (NRBCs) are premature erythrocyte precursors that reside in the bone marrow of humans of all ages as an element of erythropoiesis. They rarely present in healthy adults’ circulatory systems but can be found circulating in fetuses and neonates. An [...] Read more.
Nucleated red blood cells (NRBCs) are premature erythrocyte precursors that reside in the bone marrow of humans of all ages as an element of erythropoiesis. They rarely present in healthy adults’ circulatory systems but can be found circulating in fetuses and neonates. An NRBC count is a cost-effective laboratory test that is currently rarely used in everyday clinical practice; it is mostly used in the diagnosis of hematological diseases/disorders relating to erythropoiesis, anemia, or hemolysis. However, according to several studies, it may be used as a biomarker in the diagnosis and clinical outcome prognosis of preterm infants or severely ill adult patients. This would allow for a quick diagnosis of life-threatening conditions and the prediction of a possible change in a patient’s condition, especially in relation to patients in the intensive care unit. In this review, we sought to summarize the possible use of NRBCs as a prognostic marker in various disease entities. Research into the evaluation of the NRBCs in the pediatric population most often concerns neonatal hypoxia, the occurrence and consequences of asphyxia, and overall neonatal mortality. Among adults, NRBCs can be used to predict changes in clinical condition and mortality in critically ill patients, including those with sepsis, trauma, ARDS, acute pancreatitis, or severe cardiovascular disease. Full article
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14 pages, 2766 KiB  
Article
The Effect of the Donor’s and Recipient’s Sex on Red Blood Cells Evaluated Using Transfusion Simulations
by Emmanuel Laengst, David Crettaz, Jean-Daniel Tissot and Michel Prudent
Cells 2023, 12(11), 1454; https://doi.org/10.3390/cells12111454 - 23 May 2023
Viewed by 1033
Abstract
The hypothesis of the potential impact of the sex of red blood cell (RBC) concentrate (RCC) donors, as well as the sex of the recipients, on the clinical outcome, is still under evaluation. Here, we have evaluated the sex impact on RBC properties [...] Read more.
The hypothesis of the potential impact of the sex of red blood cell (RBC) concentrate (RCC) donors, as well as the sex of the recipients, on the clinical outcome, is still under evaluation. Here, we have evaluated the sex impact on RBC properties using in vitro transfusion models. Using a “flask model”, RBCs from RCCs (representing the donor)—at different storage lengths—were incubated in a sex-matched and sex-mismatched manner with fresh frozen plasma pools (representing the recipient) at 37 °C, with 5% of CO2 up to 48 h. Standard blood parameters, hemolysis, intracellular ATP, extracellular glucose and lactate were quantified during incubation. Additionally, a “plate model”, coupling hemolysis analysis and morphological study, was carried out in similar conditions in 96-well plates. In both models, RBCs from both sexes hemolyzed significantly less in female-derived plasma. No metabolic or morphological differences were observed between sex-matched and -mismatched conditions, even though ATP was higher in female-derived RBCs during incubations. Female plasma reduced hemolysis of female- as well as male-derived RBCs, which may be related to a sex-dependent plasma composition and/or sex-related intrinsic RBC properties. Full article
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23 pages, 7342 KiB  
Article
Analysis of Immunophenotypic Changes during Ex Vivo Human Erythropoiesis and Its Application in the Study of Normal and Defective Erythropoiesis
by Shobhita Katiyar, Arunim Shah, Khaliqur Rahman, Naresh Kumar Tripathy, Rajesh Kashyap, Soniya Nityanand and Chandra Prakash Chaturvedi
Cells 2023, 12(9), 1303; https://doi.org/10.3390/cells12091303 - 02 May 2023
Viewed by 1618
Abstract
Erythropoiesis is a highly regulated process and undergoes several genotypic and phenotypic changes during differentiation. The phenotypic changes can be evaluated using a combination of cell surface markers expressed at different cellular stages of erythropoiesis using FACS. However, limited studies are available on [...] Read more.
Erythropoiesis is a highly regulated process and undergoes several genotypic and phenotypic changes during differentiation. The phenotypic changes can be evaluated using a combination of cell surface markers expressed at different cellular stages of erythropoiesis using FACS. However, limited studies are available on the in-depth phenotypic characterization of progenitors from human adult hematopoietic stem and progenitor cells (HSPCs) to red blood cells. Therefore, using a set of designed marker panels, in the current study we have kinetically characterized the hematopoietic, erythroid progenitors, and terminally differentiated erythroblasts ex vivo. Furthermore, the progenitor stages were explored for expression of CD117, CD31, CD41a, CD133, and CD45, along with known key markers CD36, CD71, CD105, and GPA. Additionally, we used these marker panels to study the stage-specific phenotypic changes regulated by the epigenetic regulator; Nuclear receptor binding SET Domain protein 1 (NSD1) during erythropoiesis and to study ineffective erythropoiesis in myelodysplastic syndrome (MDS) and pure red cell aplasia (PRCA) patients. Our immunophenotyping strategy can be used to sort and study erythroid-primed hematopoietic and erythroid precursors at specified time points and to study diseases resulting from erythroid dyspoiesis. Overall, the current study explores the in-depth kinetics of phenotypic changes occurring during human erythropoiesis and applies this strategy to study normal and defective erythropoiesis. Full article
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13 pages, 1615 KiB  
Article
Methemoglobinemia, Increased Deformability and Reduced Membrane Stability of Red Blood Cells in a Cat with a CYB5R3 Splice Defect
by Sophia Jenni, Odette Ludwig-Peisker, Vidhya Jagannathan, Sandra Lapsina, Martina Stirn, Regina Hofmann-Lehmann, Nikolay Bogdanov, Nelli Schetle, Urs Giger, Tosso Leeb and Anna Bogdanova
Cells 2023, 12(7), 991; https://doi.org/10.3390/cells12070991 - 24 Mar 2023
Cited by 2 | Viewed by 2042
Abstract
Methemoglobinemia is an acquired or inherited condition resulting from oxidative stress or dysfunction of the NADH-cytochrome b5 reductase or associated pathways. This study describes the clinical, pathophysiological, and molecular genetic features of a cat with hereditary methemoglobinemia. Whole genome sequencing and mRNA transcript [...] Read more.
Methemoglobinemia is an acquired or inherited condition resulting from oxidative stress or dysfunction of the NADH-cytochrome b5 reductase or associated pathways. This study describes the clinical, pathophysiological, and molecular genetic features of a cat with hereditary methemoglobinemia. Whole genome sequencing and mRNA transcript analyses were performed in affected and control cats. Co-oximetry, ektacytometry, Ellman’s assay for reduced glutathione concentrations, and CYB5R activity were assessed. A young adult European domestic shorthair cat decompensated at induction of anesthesia and was found to have persistent methemoglobinemia of 39 ± 8% (reference range < 3%) of total hemoglobin which could be reversed upon intravenous methylene blue injection. The erythrocytic CYB5R activity was 20 ± 6% of normal. Genetic analyses revealed a single homozygous base exchange at the beginning of intron 3 of the CYB5R3 gene, c.226+5G>A. Subsequent mRNA studies confirmed a splice defect and demonstrated expression of two mutant CYB5R3 transcripts. Erythrocytic glutathione levels were twice that of controls. Mild microcytosis, echinocytes, and multiple Ca2+-filled vesicles were found in the affected cat. Erythrocytes were unstable at high osmolarities although highly deformable as follows from the changes in elongation index and maximal-tolerated osmolarity. Clinicopathological presentation of this cat was similar to other cats with CYB5R3 deficiency. We found that methemoglobinemia is associated with an increase in red blood cell fragility and deformability, glutathione overload, and morphological alterations typical for stress erythropoiesis. Full article
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2022

Jump to: 2024, 2023, 2021

20 pages, 4849 KiB  
Article
Membrane Properties of Human Induced Pluripotent Stem Cell-Derived Cultured Red Blood Cells
by Claudia Bernecker, Eva Maria Matzhold, Dagmar Kolb, Afrim Avdili, Lisa Rohrhofer, Annika Lampl, Martin Trötzmüller, Heike Singer, Johannes Oldenburg, Peter Schlenke and Isabel Dorn
Cells 2022, 11(16), 2473; https://doi.org/10.3390/cells11162473 - 09 Aug 2022
Cited by 3 | Viewed by 3403
Abstract
Cultured red blood cells from human induced pluripotent stem cells (cRBC_iPSCs) are a promising source for future concepts in transfusion medicine. Before cRBC_iPSCs will have entrance into clinical or laboratory use, their functional properties and safety have to be carefully validated. Due to [...] Read more.
Cultured red blood cells from human induced pluripotent stem cells (cRBC_iPSCs) are a promising source for future concepts in transfusion medicine. Before cRBC_iPSCs will have entrance into clinical or laboratory use, their functional properties and safety have to be carefully validated. Due to the limitations of established culture systems, such studies are still missing. Improved erythropoiesis in a recently established culture system, closer simulating the physiological niche, enabled us to conduct functional characterization of enucleated cRBC_iPSCs with a focus on membrane properties. Morphology and maturation stage of cRBC_iPSCs were closer to native reticulocytes (nRETs) than to native red blood cells (nRBCs). Whereas osmotic resistance of cRBC_iPSCs was similar to nRETs, their deformability was slightly impaired. Since no obvious alterations in membrane morphology, lipid composition, and major membrane associated protein patterns were observed, reduced deformability might be caused by a more primitive nature of cRBC_iPSCs comparable to human embryonic- or fetal liver erythropoiesis. Blood group phenotyping of cRBC_iPSCs further confirmed the potency of cRBC_iPSCs as a prospective device in pre-transfusional routine diagnostics. Therefore, RBC membrane analyses obtained in this study underscore the overall prospects of cRBC_iPSCs for their future application in the field of transfusion medicine. Full article
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20 pages, 1297 KiB  
Article
The Shape of Human Red Blood Cells Suspended in Autologous Plasma and Serum
by Thomas M. Fischer
Cells 2022, 11(12), 1941; https://doi.org/10.3390/cells11121941 - 16 Jun 2022
Cited by 2 | Viewed by 1932
Abstract
(1) Background: In almost all studies of the shape of the human red blood cell (RBC), the suspending medium was a salt solution supplemented with albumin. However, the ratio of thickness across the dimple region to the thickness of the rim (THR) depends [...] Read more.
(1) Background: In almost all studies of the shape of the human red blood cell (RBC), the suspending medium was a salt solution supplemented with albumin. However, the ratio of thickness across the dimple region to the thickness of the rim (THR) depends on the albumin concentration. Values of the THR in the literature range from 0.27 to 0.627 whereas in the present work it was 0.550 or 0.601 whether measured in plasma or serum. (2) Methods: 9911 RBCs of eight donors were suspended in autologous plasma or serum. Sedimented RBCs were observed under bright field illumination at 416 nm. From the profiles of gray value, the THR was determined. (3) Results: The THR displays a wide distribution within a single blood sample. A direct correlation of THR and spontaneous curvature of the membrane is likely. The variation of the mean THR between different donors is large. The aspect ratio of RBCs viewed face-on ranged on average from 1 to 1.48. In oval RBCs, the rim is thicker along the major axis than along the minor axis, an effect increasing with increasing aspect ratio. Remodeling of the membrane skeleton occurs in vivo with a characteristic time (τ) on the order of 1 h. (4) Conclusions: Consideration of these data in models of RBC behavior might improve the agreement with observations. τ1 h suggests a more general type of reference configuration of the membrane skeleton than a stress free shape. Full article
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15 pages, 1714 KiB  
Article
Interspecies Diversity of Osmotic Gradient Deformability of Red Blood Cells in Human and Seven Vertebrate Animal Species
by Adam Varga, Adam Attila Matrai, Barbara Barath, Adam Deak, Laszlo Horvath and Norbert Nemeth
Cells 2022, 11(8), 1351; https://doi.org/10.3390/cells11081351 - 15 Apr 2022
Cited by 8 | Viewed by 2056
Abstract
Plasma and blood osmolality values show interspecies differences and are strictly regulated. The effect of these factors also has an influence on microrheological parameters, such as red blood cell (RBC) deformability and aggregation. However, little is known about the interspecies differences in RBC [...] Read more.
Plasma and blood osmolality values show interspecies differences and are strictly regulated. The effect of these factors also has an influence on microrheological parameters, such as red blood cell (RBC) deformability and aggregation. However, little is known about the interspecies differences in RBC deformability at various blood osmolality levels (osmotic gradient RBC deformability). Our aim was to conduct a descriptive–comparative study on RBC osmotic gradient deformability in several vertebrate species and human blood. Blood samples were taken from healthy volunteers, dogs, cats, pigs, sheep, rabbits, rats, and mice, to measure hematological parameters, as well as conventional and osmotic gradient RBC deformability. Analyzing the elongation index (EI)–osmolality curves, we found the highest maximal EI values (EI max) in human, dog, and rabbit samples. The lowest EI max values were seen in sheep and cat samples, in addition to a characteristic leftward shift of the elongation index–osmolality curves. We found significant differences in the hyperosmolar region. A correlation of mean corpuscular volume and mean corpuscular hemoglobin concentration with osmoscan parameters was found. Osmotic gradient deformability provides further information for better exploration of microrheological diversity between species and may help to better understand the alterations caused by osmolality changes in various disorders. Full article
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19 pages, 4239 KiB  
Article
Continuous Percoll Gradient Centrifugation of Erythrocytes—Explanation of Cellular Bands and Compromised Age Separation
by Felix Maurer, Thomas John, Asya Makhro, Anna Bogdanova, Giampaolo Minetti, Christian Wagner and Lars Kaestner
Cells 2022, 11(8), 1296; https://doi.org/10.3390/cells11081296 - 11 Apr 2022
Cited by 6 | Viewed by 4860
Abstract
(1) Background: When red blood cells are centrifuged in a continuous Percoll-based density gradient, they form discrete bands. While this is a popular approach for red blood cell age separation, the mechanisms involved in banding were unknown. (2) Methods: Percoll centrifugations of red [...] Read more.
(1) Background: When red blood cells are centrifuged in a continuous Percoll-based density gradient, they form discrete bands. While this is a popular approach for red blood cell age separation, the mechanisms involved in banding were unknown. (2) Methods: Percoll centrifugations of red blood cells were performed under various experimental conditions and the resulting distributions analyzed. The age of the red blood cells was measured by determining the protein band 4.1a to 4.1b ratio based on western blots. Red blood cell aggregates, so-called rouleaux, were monitored microscopically. A mathematical model for the centrifugation process was developed. (3) Results: The red blood cell band pattern is reproducible but re-centrifugation of sub-bands reveals a new set of bands. This is caused by red blood cell aggregation. Based on the aggregation, our mathematical model predicts the band formation. Suppression of red blood cell aggregation reduces the band formation. (4) Conclusions: The red blood cell band formation in continuous Percoll density gradients could be explained physically by red blood cell aggregate formation. This aggregate formation distorts the density-based red blood cell age separation. Suppressing aggregation by osmotic swelling has a more severe effect on compromising the RBC age separation to a higher degree. Full article
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8 pages, 936 KiB  
Article
Concomitant Hereditary Spherocytosis and Pyruvate Kinase Deficiency in a Spanish Family with Chronic Hemolytic Anemia: Contribution of Laser Ektacytometry to Clinical Diagnosis
by Joan-Lluis Vives Corrons, Elena Krishnevskaya, Laura Montllor, Valentina Leguizamon and Marta Garcia Bernal
Cells 2022, 11(7), 1133; https://doi.org/10.3390/cells11071133 - 28 Mar 2022
Cited by 2 | Viewed by 1776
Abstract
Background: Hereditary spherocytosis (HS) and pyruvate kinase deficiency (PKD) are the most common causes of hereditary chronic hemolytic anemia. Here, we describe clinical and genetic characteristics of a Spanish family with concomitant β-spectrin (SPTB) c.647G>A variant and pyruvate kinase (PKLR) c.1706G>A variant. Methods: [...] Read more.
Background: Hereditary spherocytosis (HS) and pyruvate kinase deficiency (PKD) are the most common causes of hereditary chronic hemolytic anemia. Here, we describe clinical and genetic characteristics of a Spanish family with concomitant β-spectrin (SPTB) c.647G>A variant and pyruvate kinase (PKLR) c.1706G>A variant. Methods: A family of 11 members was studied. Hematological investigation, hemolysis tests, and specific red cell studies were performed in all family members, according to conventional procedures. An ektacytometric study was performed using the osmoscan module of the Lorca ektacytometer (MaxSis. RR Mechatronics). The presence of the SPTB and PKLR variants was confirmed by t-NGS. Results: The t-NGS genetic characterization of the 11 family members showed the presence of a heterozygous mutation for the β-spectrin (SPTB; c.647G>A) in seven members with HS, three of them co-inherited the PKLR variant c.1706G>A. In the remaining four members, no gene mutation was found. Ektacytometry allowed a clear diagnostic orientation of HS, independently from the PKLR variant. Conclusions: This family study allows concluding that the SPTB mutation, (c.647G>A) previously described as likely pathogenic (LP), should be classified as pathogenic (P), according to the recommendations for pathogenicity of the American College of Medical Genetics and the Association for Molecular Pathology. In addition, after 6 years of clinical follow-up of the patients with HS, it can be inferred that the chronic hemolytic anemia may be attributable to the SPTB mutation only, without influence of the concomitant PKLR. Moreover, only the family members with the SPTB mutation exhibited an ektacytometric profile characteristic of HS. Full article
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21 pages, 5668 KiB  
Article
In Vitro Erythropoiesis at Different pO2 Induces Adaptations That Are Independent of Prior Systemic Exposure to Hypoxia
by Greta Simionato, Antonia Rabe, Joan Sebastián Gallego-Murillo, Carmen van der Zwaan, Arie Johan Hoogendijk, Maartje van den Biggelaar, Giampaolo Minetti, Anna Bogdanova, Heimo Mairbäurl, Christian Wagner, Lars Kaestner and Emile van den Akker
Cells 2022, 11(7), 1082; https://doi.org/10.3390/cells11071082 - 23 Mar 2022
Cited by 1 | Viewed by 2515
Abstract
Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. At high altitude, EPO levels first increase and then decrease, although erythropoiesis remains elevated at a stable level. The roles of hypoxia and related EPO adjustments are not fully understood, which has [...] Read more.
Hypoxia is associated with increased erythropoietin (EPO) release to drive erythropoiesis. At high altitude, EPO levels first increase and then decrease, although erythropoiesis remains elevated at a stable level. The roles of hypoxia and related EPO adjustments are not fully understood, which has contributed to the formulation of the theory of neocytolysis. We aimed to evaluate the role of oxygen exclusively on erythropoiesis, comparing in vitro erythroid differentiation performed at atmospheric oxygen, a lower oxygen concentration (three percent oxygen) and with cultures of erythroid precursors isolated from peripheral blood after a 19-day sojourn at high altitude (3450 m). Results highlight an accelerated erythroid maturation at low oxygen and more concave morphology of reticulocytes. No differences in deformability were observed in the formed reticulocytes in the tested conditions. Moreover, hematopoietic stem and progenitor cells isolated from blood affected by hypoxia at high altitude did not result in different erythroid development, suggesting no retention of a high-altitude signature but rather an immediate adaptation to oxygen concentration. This adaptation was observed during in vitro erythropoiesis at three percent oxygen by a significantly increased glycolytic metabolic profile. These hypoxia-induced effects on in vitro erythropoiesis fail to provide an intrinsic explanation of the concept of neocytolysis. Full article
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2021

Jump to: 2024, 2023, 2022

13 pages, 1504 KiB  
Article
Different Involvement of Band 3 in Red Cell Deformability and Osmotic Fragility—A Comparative GP.Mur Erythrocyte Study
by Mei-Shin Kuo, Cheng-Hsi Chuang, Han-Chih Cheng, Hui-Ru Lin, Jong-Shyan Wang and Kate Hsu
Cells 2021, 10(12), 3369; https://doi.org/10.3390/cells10123369 - 30 Nov 2021
Cited by 7 | Viewed by 2141
Abstract
GP.Mur is a clinically important red blood cell (RBC) phenotype in Southeast Asia. The molecular entity of GP.Mur is glycophorin B-A-B hybrid protein that promotes band 3 expression and band 3–AQP1 interaction, and alters the organization of band 3 complexes with Rh/RhAG complexes. [...] Read more.
GP.Mur is a clinically important red blood cell (RBC) phenotype in Southeast Asia. The molecular entity of GP.Mur is glycophorin B-A-B hybrid protein that promotes band 3 expression and band 3–AQP1 interaction, and alters the organization of band 3 complexes with Rh/RhAG complexes. GP.Mur+ RBCs are more resistant to osmotic stress. To explore whether GP.Mur+ RBCs could be structurally more resilient, we compared deformability and osmotic fragility of fresh RBCs from 145 adults without major illness (47% GP.Mur). We also evaluated potential impacts of cellular and lipid factors on RBC deformability and osmotic resistivity. Contrary to our anticipation, these two physical properties were independent from each other based on multivariate regression analyses. GP.Mur+ RBCs were less deformable than non-GP.Mur RBCs. We also unexpectedly found 25% microcytosis in GP.Mur+ female subjects (10/40). Both microcytosis and membrane cholesterol reduced deformability, but the latter was only observed in non-GP.Mur and not GP.Mur+ normocytes. The osmotic fragility of erythrocytes was not affected by microcytosis; instead, larger mean corpuscular volume (MCV) increased the chances of hypotonic burst. From comparison with GP.Mur+ RBCs, higher band 3 expression strengthened the structure of RBC membrane and submembranous cytoskeletal networks and thereby reduced cell deformability; stronger band 3–AQP1 interaction additionally supported osmotic resistance. Thus, red cell deformability and osmotic resistivity involve distinct structural–functional roles of band 3. Full article
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18 pages, 1649 KiB  
Article
Causes of Anemia in Polish Older Population—Results from the PolSenior Study
by Arkadiusz Styszyński, Jerzy Chudek, Małgorzata Mossakowska, Krzysztof Lewandowski, Monika Puzianowska-Kuźnicka, Alicja Klich-Rączka, Andrzej Więcek and Katarzyna Wieczorowska-Tobis
Cells 2021, 10(8), 2167; https://doi.org/10.3390/cells10082167 - 22 Aug 2021
Cited by 8 | Viewed by 3413
Abstract
Vitamin B12, folate, iron deficiency (IDA), chronic kidney disease (CKD), and anemia of inflammation (AI) are among the main causes of anemia in the elderly. WHO criteria of nutritional deficiencies neglect aging-related changes in absorption, metabolism, and utilization of nutrients. Age-specific [...] Read more.
Vitamin B12, folate, iron deficiency (IDA), chronic kidney disease (CKD), and anemia of inflammation (AI) are among the main causes of anemia in the elderly. WHO criteria of nutritional deficiencies neglect aging-related changes in absorption, metabolism, and utilization of nutrients. Age-specific criteria for the diagnosis of functional nutritional deficiency related to anemia are necessary. We examined the nationally representative sample of Polish seniors. Complete blood count, serum iron, ferritin, vitamin B12, folate, and renal parameters were assessed in 3452 (1632 women, 1820 men) participants aged above 64. Cut-off points for nutritional deficiencies were determined based on the WHO criteria (method-A), lower 2.5 percentile of the studied population (method-B), and receiver operating characteristic (ROC) analysis (method-C). Method-A leads to an overestimation of the prevalence of vitamin B12 and folate deficiency, while method-B to their underestimation with over 50% of unexplained anemia. Based on method-C, anemia was classified as nutritional in 55.9%. In 22.3% of cases, reasons for anemia remained unexplained, the other 21.8% were related to CKD or AI. Mild cases were less common in IDA, and more common in non-deficiency anemia. Serum folate had an insignificant impact on anemia. It is necessary to adopt the age-specific criteria for nutrient deficiency in an old population. Full article
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11 pages, 8846 KiB  
Article
Effects of Genotypes and Treatment on Oxygenscan Parameters in Sickle Cell Disease
by Camille Boisson, Minke A. E. Rab, Elie Nader, Céline Renoux, Celeste Kanne, Jennifer Bos, Brigitte A. van Oirschot, Philippe Joly, Romain Fort, Alexandra Gauthier, Emeric Stauffer, Solene Poutrel, Kamila Kebaili, Giovanna Cannas, Nathalie Garnier, Cécile Renard, Olivier Hequet, Arnaud Hot, Yves Bertrand, Richard van Wijk, Vivien A. Sheehan, Eduard J. van Beers and Philippe Connesadd Show full author list remove Hide full author list
Cells 2021, 10(4), 811; https://doi.org/10.3390/cells10040811 - 05 Apr 2021
Cited by 10 | Viewed by 2525
Abstract
(1) Background: The aim of the present study was to compare oxygen gradient ektacytometry parameters between sickle cell patients of different genotypes (SS, SC, and S/β+) or under different treatments (hydroxyurea or chronic red blood cell exchange). (2) Methods: Oxygen gradient [...] Read more.
(1) Background: The aim of the present study was to compare oxygen gradient ektacytometry parameters between sickle cell patients of different genotypes (SS, SC, and S/β+) or under different treatments (hydroxyurea or chronic red blood cell exchange). (2) Methods: Oxygen gradient ektacytometry was performed in 167 adults and children at steady state. In addition, five SS patients had oxygenscan measurements at steady state and during an acute complication requiring hospitalization. (3) Results: Red blood cell (RBC) deformability upon deoxygenation (EImin) and in normoxia (EImax) was increased, and the susceptibility of RBC to sickle upon deoxygenation was decreased in SC patients when compared to untreated SS patients older than 5 years old. SS patients under chronic red blood cell exchange had higher EImin and EImax and lower susceptibility of RBC to sickle upon deoxygenation compared to untreated SS patients, SS patients younger than 5 years old, and hydroxyurea-treated SS and SC patients. The susceptibility of RBC to sickle upon deoxygenation was increased in the five SS patients during acute complication compared to steady state, although the difference between steady state and acute complication was variable from one patient to another. (4) Conclusions: The present study demonstrates that oxygen gradient ektacytometry parameters are affected by sickle cell disease (SCD) genotype and treatment. Full article
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18 pages, 36344 KiB  
Article
Acanthocyte Sedimentation Rate as a Diagnostic Biomarker for Neuroacanthocytosis Syndromes: Experimental Evidence and Physical Justification
by Alexis Darras, Kevin Peikert, Antonia Rabe, François Yaya, Greta Simionato, Thomas John, Anil Kumar Dasanna, Semen Buvalyy, Jürgen Geisel, Andreas Hermann, Dmitry A. Fedosov, Adrian Danek, Christian Wagner and Lars Kaestner
Cells 2021, 10(4), 788; https://doi.org/10.3390/cells10040788 - 02 Apr 2021
Cited by 16 | Viewed by 4704
Abstract
(1) Background: Chorea-acanthocytosis and McLeod syndrome are the core diseases among the group of rare neurodegenerative disorders called neuroacanthocytosis syndromes (NASs). NAS patients have a variable number of irregularly spiky erythrocytes, so-called acanthocytes. Their detection is a crucial but error-prone parameter in the [...] Read more.
(1) Background: Chorea-acanthocytosis and McLeod syndrome are the core diseases among the group of rare neurodegenerative disorders called neuroacanthocytosis syndromes (NASs). NAS patients have a variable number of irregularly spiky erythrocytes, so-called acanthocytes. Their detection is a crucial but error-prone parameter in the diagnosis of NASs, often leading to misdiagnoses. (2) Methods: We measured the standard Westergren erythrocyte sedimentation rate (ESR) of various blood samples from NAS patients and healthy controls. Furthermore, we manipulated the ESR by swapping the erythrocytes and plasma of different individuals, as well as replacing plasma with dextran. These measurements were complemented by clinical laboratory data and single-cell adhesion force measurements. Additionally, we followed theoretical modeling approaches. (3) Results: We show that the acanthocyte sedimentation rate (ASR) with a two-hour read-out is significantly prolonged in chorea-acanthocytosis and McLeod syndrome without overlap compared to the ESR of the controls. Mechanistically, through modern colloidal physics, we show that acanthocyte aggregation and plasma fibrinogen levels slow down the sedimentation. Moreover, the inverse of ASR correlates with the number of acanthocytes (R2=0.61, p=0.004). (4) Conclusions: The ASR/ESR is a clear, robust and easily obtainable diagnostic marker. Independently of NASs, we also regard this study as a hallmark of the physical view of erythrocyte sedimentation by describing anticoagulated blood in stasis as a percolating gel, allowing the application of colloidal physics theory. Full article
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