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Insights into Red Blood Cell Aging: In Vivo and in Vitro

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A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 16728

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Special Issue Editor

Dr. Gregory Barshtein

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Guest Editor

Biochemistry Department, The Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 9112102, Israel
Interests: red blood cells; RBC deformability; RBC fragility; RBC storage; biorheology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The aging of red blood cells (RBCs), both in vivo and in vitro, is a multifaceted biological phenomenon that is considered an issue of special scientific and clinical interest. Oxidative stress and defective adenosine triphosphate metabolism are the main driving forces of RBC alterations. Aging-related processes lead to significant metabolic and structural erythrocyte changes, including global biochemical and biophysical alteration, and remodeling of the cell membrane and cytoplasm composition, and, as a result, provoke deterioration in erythrocyte functionality and clearance of senescent cells.

For this Special Issue, we encourage original research submissions and reviews. We expect to receive contributions addressing biophysical, biochemical, and physiological aspects of RBC aging in vivo and in vitro. Analyses and evaluations of the diverse senescence markers of erythrocyte aging are also welcome. These issues will be discussed as simulations, or from a clinical or experimental point of view.

Dr. Gregory Barshtein
Guest Editors

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Keywords

Red blood cells
Erythrocytes RBC Aging
RBC Storage
RBC Clearance
RBC Lesion
Oxidative Stress Aging-related processes
Biophysical, biochemical, and physiological alteration
Clinical and experimental analysis
evaluation and simulation

Published Papers (5 papers)

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Research

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10 pages, 2498 KiB

Open AccessArticle

Effect of Red Blood Cell Aging In Vivo on Their Aggregation Properties In Vitro: Measurements with Laser Tweezers

by Petr Ermolinskiy, Andrei Lugovtsov, François Yaya, Kisung Lee, Lars Kaestner, Christian Wagner and Alexander Priezzhev

Appl. Sci. 2020, 10(21), 7581; https://doi.org/10.3390/app10217581 - 28 Oct 2020

Cited by 16 | Viewed by 3376

Abstract

Red blood cell (RBC) aggregation highly influences hemorheology and blood microcirculation in the human body. The aggregation properties of RBCs can vary due to numerous factors, including RBC age. The aim of this work was to estimate in vitro the differences in the RBC aggregation properties of different RBC age populations in single-cell experiments using laser tweezers. RBCs from five healthy volunteers were separated into four subpopulations by Percoll density gradient centrifugation. Each subpopulation of the RBC was separately resuspended in autologous plasma or dextran 70 kDa (50 mg/mL). The aggregation force between the single cells was measured with holographic laser tweezers. The obtained data demonstrated an enhancement of RBC aggregation force in doublets with age: the older the cells, the higher the aggregation force. The obtained data revealed the differences between the aggregation and aggregability of RBC in dependence of the RBC in vivo age. Full article

(This article belongs to the Special Issue Insights into Red Blood Cell Aging: In Vivo and in Vitro)

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27 pages, 8924 KiB

Open AccessArticle

Modelling of Red Blood Cell Morphological and Deformability Changes during In-Vitro Storage

by Nadeeshani Geekiyanage, Emilie Sauret, Suvash Saha, Robert Flower and YuanTong Gu

Appl. Sci. 2020, 10(9), 3209; https://doi.org/10.3390/app10093209 - 04 May 2020

Cited by 13 | Viewed by 4849

Abstract

Storage lesion is a critical issue facing transfusion treatments, and it adversely affects the quality and viability of stored red blood cells (RBCs). RBC deformability is a key indicator of cell health. Deformability measurements of each RBC unit are a key challenge in transfusion medicine research and clinical haematology. In this paper, a numerical study, inspired from the previous research for RBC deformability and morphology predictions, is conducted for the first time, to investigate the deformability and morphology characteristics of RBCs undergoing storage lesion. This study investigates the evolution of the cell shape factor, elongation index and membrane spicule details, where applicable, of discocyte, echinocyte I, echinocyte II, echinocyte III and sphero-echinocyte morphologies during 42 days of in-vitro storage at 4 °C in saline-adenine-glucose-mannitol (SAGM). Computer simulations were performed to investigate the influence of storage lesion-induced membrane structural defects on cell deformability and its recoverability during optical tweezers stretching deformations. The predicted morphology and deformability indicate decreasing quality and viability of stored RBCs undergoing storage lesion. The loss of membrane structural integrity due to the storage lesion further degrades the cell deformability and recoverability during mechanical deformations. This numerical approach provides a potential framework to study the RBC deformation characteristics under varying pathophysiological conditions for better diagnostics and treatments. Full article

(This article belongs to the Special Issue Insights into Red Blood Cell Aging: In Vivo and in Vitro)

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9 pages, 1255 KiB

Open AccessArticle

The Contribution of Storage Medium and Membranes in the Microwave Dielectric Response of Packed Red Blood Cells Suspension

by Larisa Latypova, Gregory Barshtein, Dan Arbell and Yuri Feldman

Appl. Sci. 2020, 10(5), 1702; https://doi.org/10.3390/app10051702 - 02 Mar 2020

Cited by 2 | Viewed by 2121

Abstract

During cold storage, packed red blood cells (PRBCs) undergo slow detrimental changes that are collectively termed storage lesion. The aging of the cells causes alterations in the composition of the storage-medium in the PRBC unit. In this paper, we present the comparison of the dielectric response of water in the primary (fresh) storage medium (citrate phosphate dextrose adenine solution, CPDA-1) versus the storage medium from three expired units of PRBCs. Dielectric response of the water molecules has been characterized by dielectric spectroscopy technique in the microwave frequency band (0.5–40 GHz). The dominant phenomenon is the significant increase of the dielectric strength and decrease the relaxation time τ for the samples of the stored medium in comparison with the fresh medium CPDA-1. Furthermore, we demonstrated that removing the ghosts from PRBC hemolysate did not cause the alteration of the dielectric spectrum of water. Thus, the contribution associated with water located near the cell membrane can be neglected in microwave dielectric measurements. Full article

(This article belongs to the Special Issue Insights into Red Blood Cell Aging: In Vivo and in Vitro)

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8 pages, 1843 KiB

Open AccessFeature PaperArticle

Red Blood Cell Aging as a Homeostatic Response to Exercise-Induced Stress

by Joames K. Freitas Leal, Dan Lazari, Coen C.W.G. Bongers, Maria T.E. Hopman, Roland Brock and Giel J.C.G.M. Bosman

Appl. Sci. 2019, 9(22), 4827; https://doi.org/10.3390/app9224827 - 11 Nov 2019

Cited by 3 | Viewed by 3152

Abstract

Our knowledge on the molecular mechanisms of red blood cell aging is mostly derived from in vitro studies. The Four Days Marches of Nijmegen in the Netherlands, the world’s largest yearly walking event, constitutes a unique possibility to study the effect of mechanical and biochemical stressors occurring during moderate-intensity exercise on red blood cell aging in vivo. Therefore, longitudinal measurements were performed of biophysical, immunological, and functional red blood cell characteristics that are known to change during aging. Our data show that moderate-intensity exercise induces the generation of a functionally improved red blood cell population with a higher deformability and a decreased tendency to aggregate. This is likely to be associated with an early removal of the oldest red blood cells from the circulation, as deduced from the (dis)appearance of removal signals. Thus, the physiological red blood cell aging process maintains homeostasis in times of moderate-intensity exercise-induced stress, probably by accelerated aging and subsequent removal of the oldest, most vulnerable red blood cells. Full article

(This article belongs to the Special Issue Insights into Red Blood Cell Aging: In Vivo and in Vitro)

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Review

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13 pages, 1180 KiB

Open AccessReview

RBC Storage Lesion Studies in Humans and Experimental Models of Shock

by Willard N. Applefeld, Jeffrey Wang, Steven B. Solomon, Junfeng Sun, Harvey G. Klein and Charles Natanson

Appl. Sci. 2020, 10(5), 1838; https://doi.org/10.3390/app10051838 - 07 Mar 2020

Cited by 1 | Viewed by 2465

Abstract

The finding of toxicity in a meta-analysis of observational clinical studies of transfused longer stored red blood cells (RBC) and ethical issues surrounding aging blood for human studies prompted us to develop an experimental model of RBC transfusion. Transfusing older RBCs during canine pneumonia increased mortality rates. Toxicity was associated with in vivo hemolysis with release of cell-free hemoglobin (CFH) and iron. CFH can scavenge nitric oxide, causing vasoconstriction and endothelial injury. Iron, an essential bacterial nutrient, can worsen infections. This toxicity was seen at commonly transfused blood volumes (2 units) and was altered by the severity of pneumonia. Washing longer-stored RBCs mitigated these detrimental effects, but washing fresh RBCs actually increased them. In contrast to septic shock, transfused longer stored RBCs proved beneficial in hemorrhagic shock by decreasing reperfusion injury. Intravenous iron was equivalent in toxicity to transfusion of longer stored RBCs and both should be avoided during infection. Storage of longer-stored RBCs at 2 °C instead of higher standard temperatures (4–6 °C) minimized the release of CFH and iron. Haptoglobin, a plasma protein that binds CFH and increases its clearance, minimizes the toxic effects of longer-stored RBCs during infection and is a biologically plausible novel approach to treat septic shock. Full article

(This article belongs to the Special Issue Insights into Red Blood Cell Aging: In Vivo and in Vitro)

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