Lars Kaestner

• Prof. Dr. rer. nat.
• PI at Saarland University

Centrifugation of biological matter in density gradient solutions is a standard method for separating cell types or components. It is also used to separate red blood cells (RBCs) by age, as they lose water and become denser over their lifespan. When the density gradient is prepared with Percoll, discrete bands of RBCs are systematically observed al...

The core neuroacanthocytosis syndromes, i.e., chorea-acanthocytosis/VPS13A disease (ChAc) and McLeod syndrome/XK disease (MLS), are respectively due to mutations in VPS13A and XK genes and share similar manifestations including the formation of acanthocytes. We previously showed by lipidomics of red blood cells (RBCs) from ChAc patients slight lipi...

The article provides a comprehensive overview of biological membrane lipid composition and distribution and ion transport processes, focusing particularly on red blood cells (RBCs). It begins with a historical perspective, detailing the introduction of the terms ‘cell’ and ‘membrane’ in biological sciences, and the development of the fluid-mosaic m...

In the age of "omics", lipidomics of erythropoiesis is still missing. How reticulocytes mature in the circulation into functional erythrocytes is also largely unknown. We have isolated here two populations of human circulating reticulocytes at different levels of maturation, and three subpopulations of erythrocytes of different age, and characteriz...

Deletion of the short arm of chromosome 1 (1p) increases recurrence rates in meningiomas by up to 33%, regardless of tumor grade, correlating with absence of intracellular alkaline phosphatase enzyme activity. Current screening methods for 1p deletion like fluorescence in situ hybridization (FISH) and loss of heterozygosity (LOH) analysis are resou...

Channelrhodopsins (ChRs) are light-gated ion channels originally discovered in algae and are commonly used in neuroscience for controlling the electrical activity of neurons with high precision. Initially-discovered ChRs were non-selective cation channels, allowing the flow of multiple ions, such as Na+, K+, H+, and Ca2+, leading to membrane depola...

The erythrocyte sedimentation rate (ESR) is one of the oldest diagnostic tools already known by the ancient Greeks. When blood is placed in a tube, a phase separation between blood plasma and the remaining part of the blood containing the cells appears. The distance between the top of the liquid and the phase boundary determines the sedimentation h...

Evaporation of blood droplets and diluted blood samples is a topic of intensive research, as it is considered a potential low-cost diagnostic tool. So far, samples with a volume fraction down to a few percent of red blood cells have been studied, and these were reportedly dominated by a “coffee-ring” deposit. In this study, samples with lower volum...

Introduction The unique red blood cell (RBC) properties that characterize the rare neuroacanthocytosis syndromes (NAS) have prompted the exploration of osmotic gradient ektacytometry (Osmoscan) as a diagnostic tool for these disorders. In this exploratory study, we assessed if Osmoscans can discriminate NAS from other neurodegenerative diseases. M...

Centrifugation of erythrocytes (aka Red Blood Cells, RBCs) in a self-forming Percoll gradient is a protocol often used as a way to sort RBCs by age. However, a pattern formation of discrete bands is systematically observed along the continuous density gradient. Although early studies mentioned that aggregation between cells might modify their spati...

Evaporation of blood droplets and diluted blood samples is a topic of intensive research, as it is seen as a possible low-cost tool for diagnosis. So far, samples with volume fraction down to a few percents of Red Blood Cells (RBCs) have been studied, and those were reportedly dominated by a ``coffee-ring'' deposit. In this study, samples with lowe...

We investigated highlanders, permanently living at an altitude of 5100 m and compared Chronic Mountain Sickness (CMS) patients with control volunteers. While we found differences in systemic parameters such as blood oxygen content, hematocrit, hemoglobin concentration, and blood viscosity, the mechanical and rheological properties of single red blo...

Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradict...

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 [...]

La Rinconada ist mit einer Höhe von 5000–5300 m über dem Meeresspiegel die höchstgelegene dauerhaft bewohnte Stadt unserer Erde (Abb. 1, 2). Die Goldgräberstadt liegt im Süden Perus, gerade mal 2,5 Autostunden vom Titicacasee entfernt. Seit 2018 führt das französische Institut für Gesundheit und medizinische Forschung an der Universität Grenoble-Al...

The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood. Here, we use state-of-the-art biochemical methods to probe for the abundance of the channels in RBCs. Furthermore,...

Red blood cell (RBC) metabolic reprogramming upon exposure to high altitude contributes to physiological human adaptations to hypoxia, a multifaceted process critical to health and disease. To delve into the molecular underpinnings of this phenomenon, first, we performed a multi-omics analysis of RBCs from six lowlanders after exposure to high-alti...

Erythrocyte Sedimentation Rate (ESR) is a clinical parameter used as a non-specific marker for inflammation, and recent studies have shown that it is linked to the collapse of the gel formed by red blood cells (RBCs) at physiological hematocrits (i.e. RBC volume fraction). Previous research has suggested that the observation of a slower initial dyn...

The 11th International Meeting on Neuroacanthocytosis Syndromes was held on September 15th–17th, 2023 at the University Hospital Campus in Homburg/Saar, Germany. The meeting followed the previous ten international symposia, the last of which was held online due to restrictions due to COVID19, in March 2021. The setting of the meeting encouraged int...

(1) Background: The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood.; (2) Methods: Here we use state-of-the-art biochemical methods to probe for the abundance of the c...

THC triggers a pronounced entry of Ca²⁺, which may be deleterious, into sickle cell red blood cells via activation of the TRPV2 channel. image

PIEZO1 channels are mechanically activated cation channels that play a pivotal role in sensing mechanical forces in various cell types. Their dysfunction has been associated with numerous pathophysiological states, including generalized lymphatic dysplasia, varicose vein disease, and hereditary xerocytosis. Given their physiological relevance, inve...

Adenosine Triphosphatase (ATPase) Phospholipid Transporting 11C gene (ATP11C) encodes the major phosphatidylserine (PS) flippase in human red blood cells (RBCs). Flippases actively transport phospholipids (e.g., PS) from the outer to the inner leaflet to establish and maintain phospholipid asymmetry of the lipid bilayer of cell membranes. This asym...

Erythrocyte Sedimentation Rate (ESR) is a clinical parameter used as a non-specific marker for inflammation, and recent studies have shown that it is linked to the collapse of the gel formed by red blood cells (RBCs) at physiological hematocrits (i.e. RBC volume fraction). Previous research has suggested that the delay time before the sedimentation...

In the age of "omics", lipidomics of erythropoiesis is still missing. How reticulocytes mature in the circulation into functional erythrocytes is also largely unknown, beyond the lipidomics level. We have isolated here two populations of human circulating reticulocytes at different levels of maturation, and three subpopulations of erythrocytes of d...

Blood flow in the microcirculatory system is crucially affected by intrinsic red blood cell (RBC) properties, such as their deformability. In the smallest vessels of this network, RBCs adapt their shapes to the flow conditions. Although it is known that the age of RBCs modifies their physical properties, such as increased cytosol viscosity and alte...

Background: "Artificial intelligence" and "big data" increasingly take the step from just being interesting concepts to being relevant or even part of our lives. This general statement holds also true for transfusion medicine. Besides all advancements in transfusion medicine, there is not yet an established red blood cell quality measure, which is...

Red blood cells (or erythrocytes) sedimentation rate (ESR) is a physical derived parameter of blood which is often used in routine health checks and medical diagnosis. Indeed, in case of inflammation, a higher ESR is observed due to the associated increase in fibrinogen and other plasma proteins. It was believed that this increase is due to the for...

The distribution of red blood cells (RBCs) in the microcirculation determines the oxygen delivery and solute transport to tissues. This process relies on the partitioning of RBCs at successive bifurcations throughout the microvascular network and it is known since the last century that RBCs partition disproportionately to the fractional blood flow...

Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can affect multiple organs, among which is the circulatory system. Inflammation and mortality risk markers were previously detected in COVID-19 plasma and red blood cells (RBCs) metabolic and proteomic profiles. Additionally, biophy...

For some molecular players in red blood cells, the functional indications and molecular evidence are discrepant. One such protein is transient potential receptor channel of canonical type 6 (TRPC6). Transcriptome analysis of reticulocytes revealed the presence of TRPC6 in mouse red blood cells and its absence in human red blood cells. We transfused...

Fast changes in environmental oxygen availability translate into shifts in mitochondrial free radical production. An increase in intraerythrocytic reduced glutathione (GSH) during deoxygenation would support the detoxification of exogenous oxidants released into the circulation from hypoxic peripheral tissues. Although reported, the mechanism behin...

Blood is mainly comprised of red blood cells (RBCs) that determine the unique flow properties of blood in the circulatory system. Healthy RBCs are characterized by high deformability, which enables them to dynamically adapt their shape to the flow conditions of the vessel. However, diseases, drugs, and medical treatments can affect RBC deformabilit...

The distribution of red blood cells (RBCs) in the microcirculation determines the oxygen delivery and solute transport to tissues. It is known since the last century that RBCs partition at bifurcations disproportionately to the fractional blood flow rate, leading to heterogeneity of the hematocrit (i.e. volume fraction of RBCs in blood) in microves...

Including artificial intelligence in haematological education is compulsory but should not be limited to students. Experienced haematologist and decision‐makers in the clinical environment have at least similar needs. This is because of the tremendous potential, opportunities and benefits the timely inclusion of artificial intelligence offers in di...

It is with great interest that we read the report by Trudel et al. (Nat. Med. 28, 59-62, 2022), who propose that accelerated hemolysis significantly contributes to "space anemia". The authors have monitored hematological parameters and exhaled carbon monoxide (CO) in astronauts during 5 months-long space missions on the ISS, and up to one year afte...

In many medical disciplines, red blood cells are discovered to be biomarkers since they “experience” various conditions in basically all organs of the body. Classical examples are diabetes and hypercholesterolemia. However, recently the red blood cell distribution width (RDW), is often referred to, as an unspecific parameter/marker (e.g., for cardi...

Blood is mainly comprised of red blood cells (RBCs) that determine the unique flow properties of blood in the circulatory system. In this study, we present a microfluidic-based approach to analyze the flow behavior of RBCs under confined flow conditions as they are in the microcirculation. In narrow vessels, RBCs exhibit characteristic shapes that...

(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 conditio...

Misshaped red blood cells (RBCs), characterized by thorn-like protrusions known as acanthocytes, are a key diagnostic feature in Chorea-Acanthocytosis (ChAc), a rare neurodegenerative disorder. The altered RBC morphology likely influences their biomechanical properties which are crucial for the cells to pass the microvasculature. Here, we investiga...

Extracellular vesicles (EVs) are cell-derived membrane particles that include exosomes, ectosomes, microvesicles, microparticles, apoptotic bodies, and other EV subsets. EVs are involved in intercellular communication and the transport of macromolecules between cells. Here, we propose and test the ability of red blood cell (RBC)-derived EVs (RBC-EV...

Coronavirus disease 2019 (COVID-19) is caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and can affect multiple organs, among which is the circulatory system. Inflammation and mortality risk markers were previously detected in COVID-19 plasma and red blood cells (RBCs) metabolic and proteomic profiles. Additionally, biophy...

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 neo...

The erythrocyte (or red blood cell) sedimentation rate (ESR) is commonly interpreted as a measure of cell aggregation and as a biomarker of inflammation. It is well known that an increase of fibrinogen concentration, an aggregation-inducing protein for erythrocytes, leads to an increase of the sedimentation rate of erythrocytes, which is generally...

The erythrocyte sedimentation rate is one of the oldest medical diagnostic methods whose physical mechanisms remain debatable today. Using both light microscopy and mesoscale cell-level simulations, we show that erythrocytes form a soft-particle gel. Furthermore, the high volume fraction of erythrocytes, their deformability, and weak attraction lea...

Erythrocytes represent at least 60% of all cells in the human body. During circulation, they experience a huge variety of physical and chemical stimulations, such as pressure, shear stress, hormones or osmolarity changes. These signals are translated into cellular responses through ion channels that modulate erythrocyte function. Ion channels in er...

The erythrocyte sedimentation rate (ESR) is one of the oldest medical diagnostic tools. However, currently there is some debate on the structure formed by the cells during the sedimentation process. While the conventional view is that erythrocytes sediment as separate aggregates, others have suggested that they form a percolating gel, similar to ot...

Misshaped red blood cells (RBCs), characterized by thorn-like protrusions known as acanthocytes, are a key diagnostic feature in Chorea-Acanthocytosis (ChAc), a rare neurodegenerative disorder. The altered RBC morphology likely influences their biomechanical properties which are crucial for the cells to pass the microvasculature. Here, we investiga...

ZUSAMMENFASSUNG Neozytolyse bezeichnet die bevorzugte Zerstörung von jungen roten Blutzellen (Neozyten), wenn zu viele Erythrozyten vorhanden sind. Das kommt in der Raumfahrt oder beim Abstieg nach langem Höhenaufenthalt vor. Mit dem Ziel, die Existenz von Neozytolyse erstmals zu beweisen, haben wir in der Forschungsstation Jungfraujoch (3450 Hm) e...

Background: Coronavirus disease 2019 (COVID-19) patients who need intensive medical care often require oxygen ventilation, but the number of ventilation machines is limited, and in some parts of the world, they are not available at all. In addition to patients for whom there is no access to ventilation machines there is also a considerable populati...

In patients with Gárdos channelopathy (p.R352H), an increased concentration of intracellular Ca2+ was previously reported. This is a surprising finding because the Gárdos channel (KCa3.1) is a K+ channel. Here, we confirm the increased intracellular Ca2+ for patients with the KCa3.1 mutation p.S314P. Furthermore, we provide the concept of KCa3.1 ac...

The erythrocyte sedimentation rate (ESR) is one of the oldest medical diagnostic tools. However, currently there is some debate on the structure formed by the cells during the sedimentation process. While the conventional view is that erythrocytes sediment as separate aggregates, others have suggested that they form a percolating gel, similar to ot...

The erythrocyte (or red blood cell) sedimentation rate (ESR) is commonly interpreted as a measure of cell aggregation and as a biomarker of inflammation. It is well known that an increase of fibrinogen concentration, an aggregation-inducing protein for erythrocytes, leads to an increase of the sedimentation rate of erythrocytes, which is generally...

The erythrocyte sedimentation rate is one of the oldest medical diagnostic methods whose physical mechanisms remain debatable up to date. Using both light microscopy and mesoscale cell-level simulations, we show that erythrocytes form a soft-colloid gel. Furthermore, the high volume fraction of erythrocytes, their deformability, and weak attraction...

…. commented Rice and Gunga 1 pointing to the fact that science is the interpretation of results, where it is easily possible to explain an experimental observation with different hypotheses. The more supporting parameters are measured, the more likely a hypothesis reflects the actual mechanism. Rice and Gunga 1 commented on a study by Klein et al....

In their comment, Song and colleagues 2 summarize their work on a mouse model in support of neocytolysis 3 in response to our manuscript (Klein et al. 2021) 4, where we argue against this concept 4. Therefore, we also contradict directly the work by Alfrey, Rice and colleagues 5‐7 where they first proposed this mechanism to explain the decrease in...

The investigation of cell shapes mostly relies on the manual classification of 2D images, causing a subjective and time consuming evaluation based on a portion of the cell surface. We present a dual-stage neural network architecture for analyzing fine shape details from confocal microscopy recordings in 3D. The system, tested on red blood cells, us...

Background: Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disease with deformed red blood cells (RBCs), so-called acanthocytes, as a typical marker of the disease. Erythrocyte sedimentation rate (ESR) was recently proposed as a diagnostic biomarker. To date, there is no treatment option for affected patients, but promising the...

Background: Coronavirus disease 2019 (COVID-19) patients who need intensive medical care often require oxygen ventilation, but the number of ventilation machines is limited, and in some parts of the world, they are not available at all. In addition to patients for whom there is no access to ventilation machines there is also a considerable populati...

(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 NAS...

We propose a flow cytometry concept that combines a spatial optical modulation scheme and deep learning for lensless cell imaging. Inspired by auto-encoder techniques, an artificial neural network mimics the optical transfer function of a particular microscope and camera for certain types of cells once trained and reconstructs microscope images fro...

Aims. Total haemoglobin mass (tot-Hb) increases during high altitude acclimatization. Normalization of tot-Hb upon descent is thought to occur via neocytolysis, the selective destruction of newly formed erythrocytes. Because convincing experimental proof of neocytolysis is lacking, we performed a prospective study on erythrocyte survival after a st...

The microvascular networks in the body of vertebrates consist of the smallest vessels such as arterioles, capillaries, and venules. The flow of RBCs through these networks ensures the gas exchange in as well as the transport of nutrients to the tissues. Any alterations in this blood flow may have severe implications on the health state. Since the v...

(1) Background: It is known that sickle cells contain a higher amount of Ca2+ compared to healthy red blood cells (RBCs). The increased Ca2+ is associated with the most severe symptom of sickle cell disease (SCD), the vaso-occlusive crisis (VOC). The Ca2+ entry pathway received the name of Psickle but its molecular identity remains only partly reso...