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Lab on a Chip Nov 2017Blood cells circulate in a dynamic fluidic environment, and during hematologic processes such as hemostasis, thrombosis, and inflammation, blood cells interact...
Blood cells circulate in a dynamic fluidic environment, and during hematologic processes such as hemostasis, thrombosis, and inflammation, blood cells interact biophysically with a myriad of vascular matrices-blood clots and the subendothelial matrix. While it is known that adherent cells physiologically respond to the mechanical properties of their underlying matrices, how blood cells interact with their mechanical microenvironment of vascular matrices remains poorly understood. To that end, we developed microfluidic systems that achieve high fidelity, high resolution, single-micron PDMS features that mimic the physical geometries of vascular matrices. With these electron beam lithography (EBL)-based microsystems, the physical interactions of individual blood cells with the mechanical properties of the matrices can be directly visualized. We observe that the physical presence of the matrix, in and of itself, mediates hematologic processes of the three major blood cell types: platelets, erythrocytes, and leukocytes. First, we find that the physical presence of single micron micropillars creates a shear microgradient that is sufficient to cause rapid, localized platelet adhesion and aggregation that leads to complete microchannel occlusion; this response is enhanced with the presence of fibrinogen or collagen on the micropillar surface. Second, we begin to describe the heretofore unknown biophysical parameters for the formation of schistocytes, pathologic erythrocyte fragments associated with various thrombotic microangiopathies (poorly understood, yet life-threatening blood disorders associated with microvascular thrombosis). Finally, we observe that the physical interactions with a vascular matrix is sufficient to cause neutrophils to form procoagulant neutrophil extracellular trap (NET)-like structures. By combining electron beam lithography (EBL), photolithography, and soft lithography, we thus create microfluidic devices that provide novel insight into the response of blood cells to the mechanical microenvironment of vascular matrices and have promise as research-enabling and diagnostic platforms.
Topics: Blood Cells; Cells, Cultured; Cellular Microenvironment; Dimethylpolysiloxanes; Equipment Design; Humans; Microfluidic Analytical Techniques; Models, Biological; Nylons; Platelet Activation; Thrombosis; Thrombotic Microangiopathies
PubMed: 29052682
DOI: 10.1039/c7lc00720e -
Clinical Hemorheology and... Oct 2015Red blood cell rheology and adhesiveness play a key role in the occurrence of vaso-occlusive like events in sickle cell anemia. The present paper reviews... (Review)
Review
Red blood cell rheology and adhesiveness play a key role in the occurrence of vaso-occlusive like events in sickle cell anemia. The present paper reviews counter-intuitive findings supporting that rigid and serrated sickle red blood cells do not initiate vaso-occlusion. Instead, the less rigid red blood cells could initiate vaso-occlusion because of their increased adhesiveness to the vascular wall. We suspect that stiffness of sickle erythrocytes and the topography of RBC membrane are factors affecting adhesion to the endothelium.
Topics: Anemia, Sickle Cell; Erythrocyte Membrane; Erythrocytes; Erythrocytes, Abnormal; Humans; Rheology
PubMed: 26484716
DOI: 10.3233/CH-152014 -
Analytical Chemistry Jan 2024Lead is a widespread environmental hazard that can adversely affect multiple biological functions. Blood cells are the initial targets that face lead exposure. However,...
Lead is a widespread environmental hazard that can adversely affect multiple biological functions. Blood cells are the initial targets that face lead exposure. However, a systematic assessment of lead dynamics in blood cells at single-cell resolution is still absent. Herein, C57BL/6 mice were fed with lead-contaminated food. Peripheral blood was harvested at different days. Extracted red blood cells and leukocytes were stained with 19 metal-conjugated antibodies and analyzed by mass cytometry. We quantified the time-lapse lead levels in 12 major blood cell subpopulations and established the distribution of lead heterogeneity. Our results show that the lead levels in all major blood cell subtypes follow lognormal distributions but with distinctively individual skewness. The lognormal distribution suggests a multiplicative accumulation of lead with stochastic turnover of cells, which allows us to estimate the lead lifespan of different blood cell populations by calculating the distribution skewness. These findings suggest that lead accumulation by single blood cells follows a stochastic multiplicative process.
Topics: Animals; Mice; Longevity; Lead; Mice, Inbred C57BL; Leukocytes; Erythrocytes
PubMed: 38176010
DOI: 10.1021/acs.analchem.3c03441 -
Tissue Engineering and Regenerative... Apr 2020Extracellular trap formation (ETosis) by various blood cells has been reported. This trap contains DNA, histones and granular proteins which can elicit an innate immune... (Review)
Review
BACKGROUND
Extracellular trap formation (ETosis) by various blood cells has been reported. This trap contains DNA, histones and granular proteins which can elicit an innate immune response by entrapping microorganisms. The trap thus formed has been reported to have an involvement in various pathogenic conditions as well. This review focusses on the trap formation by different blood cells, the immune response associated with trap formation and also its role in various clinical conditions.
METHOD
An extensive literature survey on ETosis by blood cells from 2003 to 2019 has been done. After going through the literature throughly, in this review we focuses on the trap formation by different blood cell types such as neutrophils, macrophages, eosinophils, basophils, mast cells, plasmacytoid dentritic cells, and monocytes. The mechanism with which it releases trap, the immune response it elicits and ultimately its involvement in various pathogenic conditions are described here. This article extensively covered all the above aspects and finally comprehends in nutshell the various stimuli that are currently known in trigerring the ETosis, its effect and ultimately its role in disease process.
RESULTS
A clarity about the extracellular trap formation by various blood cells, mechanism of ETosis, role of Etosis in microbial invasion and in various pathogenic situations by various blood cells have been described here.
CONCLUSION
The current understanding about the process of ETosis and its effects has been extensively described here. Along with lot of favourable outcomes, the process of ETosis will lead to lot of pathogenic situations including thrombosis, tumour metastasis and sepsis. Current understanding about ETosis is limited. Indepth understanding of ETosis may have great therapeutic potential in the diagnosis, guiding of therapy and prognostication in various pathogenic situations including infectious conditions, autoimmune disorders and tumors.
Topics: Autoimmune Diseases; Blood Cells; Endothelial Cells; Eosinophils; Extracellular Traps; Histones; Immunity; Immunity, Innate; Macrophages; Mast Cells; Monocytes; Neutrophils; Thrombosis
PubMed: 32114678
DOI: 10.1007/s13770-020-00241-z -
Thrombosis and Haemostasis Dec 2021The capacity of blood to form thrombin is a critical determinant of coagulability. Plasma thrombin generation (TG), a test that probes the capacity of plasma to form... (Review)
Review
The capacity of blood to form thrombin is a critical determinant of coagulability. Plasma thrombin generation (TG), a test that probes the capacity of plasma to form thrombin, has improved our knowledge of the coagulation system and shows promising utility in coagulation management. Although plasma TG gives comprehensive insights into the function of pro- and anticoagulation drivers, it does not measure the role of blood cells in TG. In this literature review, we discuss currently available continuous TG tests that can reflect the involvement of blood cells in coagulation, in particular the fluorogenic assays that allow continuous measurement in platelet-rich plasma and whole blood. We also provide an overview about the influence of blood cells on blood coagulation, with emphasis on the direct influence of blood cells on TG. Platelets accelerate the initiation and velocity of TG by phosphatidylserine exposure, granule content release and surface receptor interaction with coagulation proteins. Erythrocytes are also major providers of phosphatidylserine, and erythrocyte membranes trigger contact activation. Furthermore, leukocytes and cancer cells may be important players in cell-mediated coagulation because, under certain conditions, they express tissue factor, release procoagulant components and can induce platelet activation. We argue that testing TG in the presence of blood cells may be useful to distinguish blood cell-related coagulation disorders. However, it should also be noted that these blood cell-dependent TG assays are not clinically validated. Further standardization and validation studies are needed to explore their clinical usefulness.
Topics: Biomarkers; Blood Cells; Blood Coagulation; Blood Coagulation Tests; Blood Platelets; Erythrocytes; Humans; Leukocytes; Neoplastic Cells, Circulating; Predictive Value of Tests; Thrombin; Time Factors
PubMed: 33742437
DOI: 10.1055/a-1450-8300 -
Integrative Zoology May 2024Red-eared sliders (Trachemys scripta elegans), as one of the 100 most threatening aliens, have stronger immunity than the native species in response to environmental...
Red-eared sliders (Trachemys scripta elegans), as one of the 100 most threatening aliens, have stronger immunity than the native species in response to environmental stress. Blood cells are an important component of immunity in the body. However, the blood cell researches of turtle are still in the traditional blood cell classification and morphological structure observation. Furthermore, turtle granulocytes cannot be accurately identified using traditional methods. Single-cell RNA sequencing techniques have been successfully implemented to study cells based on the mRNA expression patterns of each cell. The present study profiled the transcriptomes of peripheral blood cells in red-eared sliders to construct a single-cell transcriptional landscape of the different cell types and explored environmental adaptation mechanism from the perspective of hematology. All 14 transcriptionally distinct clusters (platelets, erythrocytes1, erythrocytes2, CSF1R monocytes, POF1B monocytes, neutrophils, GATA2high basophils, GATA2low basophils, CD4 T cells, CD7 T cells, B cells, ACKR4 cells, serotriflin cells, and ficolin cells) were identified in the peripheral blood cells of the red-eared sliders. In particular, a subtype of erythrocytes (erythrocytes1) that expressed immune signals was identified. Peripheral blood cells were grouped into three lineages: platelet, erythroid/lymphoid, and myeloid cell lineages. Furthermore, based on differentiation trajectory and up-regulated gene expression, ACKR4 cells were newly identified as lymphocytes, and serotriflin and ficolin cells as granulocytes. The single-cell transcriptional atlas of the peripheral blood cells in red-eared sliders provided in the present study will offer a comprehensive transcriptome reference for the exploration of physiological and pathological hematology in this species.
Topics: Animals; Turtles; Transcriptome; Single-Cell Analysis; Adaptation, Physiological; Blood Cells
PubMed: 37226359
DOI: 10.1111/1749-4877.12725 -
Computers in Biology and Medicine Oct 2019Identification of genes whose regulation of expression is functionally similar in both brain tissue and blood cells could in principle enable monitoring of significant...
Identification of genes whose regulation of expression is functionally similar in both brain tissue and blood cells could in principle enable monitoring of significant neurological traits and disorders by analysis of blood samples. We thus employed transcriptional analysis of pathologically affected tissues, using agnostic approaches to identify overlapping gene functions and integrating this transcriptomic information with expression quantitative trait loci (eQTL) data. Here, we estimate the correlation of gene expression in the top-associated cis-eQTLs of brain tissue and blood cells in Parkinson's Disease (PD). We introduced quantitative frameworks to reveal the complex relationship of various biasing genetic factors in PD, a neurodegenerative disease. We examined gene expression microarray and RNA-Seq datasets from human brain and blood tissues from PD-affected and control individuals. Differentially expressed genes (DEG) were identified for both brain and blood cells to determine common DEG overlaps. Based on neighborhood-based benchmarking and multilayer network topology approaches we then developed genetic associations of factors with PD. Overlapping DEG sets underwent gene enrichment using pathway analysis and gene ontology methods, which identified candidate common genes and pathways. We identified 12 significantly dysregulated genes shared by brain and blood cells, which were validated using dbGaP (gene SNP-disease linkage) database for gold-standard benchmarking of their significance in disease processes. Ontological and pathway analyses identified significant gene ontology and molecular pathways that indicate PD progression. In sum, we found possible novel links between pathological processes in brain tissue and blood cells by examining cell pathway commonalities, corroborating these associations using well validated datasets. This demonstrates that for brain-related pathologies combining gene expression analysis and blood cell cis-eQTL is a potentially powerful analytical approach. Thus, our methodologies facilitate data-driven approaches that can advance knowledge of disease mechanisms and may, with clinical validation, enable prediction of neurological dysfunction using blood cell transcript profiling.
Topics: Biomarkers; Blood Cells; Brain; Computer Simulation; Databases, Nucleic Acid; Gene Expression Regulation; Genome-Wide Association Study; Humans; Parkinson Disease
PubMed: 31437626
DOI: 10.1016/j.compbiomed.2019.103385 -
European Journal of Haematology Sep 1990Platelet-derived growth factor (PDGF) is a family of dimeric protein molecules synthesized by differentiated, non-dividing and proliferating blood cells. Experimental... (Review)
Review
Platelet-derived growth factor (PDGF) is a family of dimeric protein molecules synthesized by differentiated, non-dividing and proliferating blood cells. Experimental findings indicate that PDGF is involved in development and/or maintenance of physiological functions of certain normal blood cells. Also, PDGF synthesis correlates with certain blood cell proliferative diseases caused either spontaneously or associated with viral infection. There is increasing evidence that the diverse effects of PDGF in both normal and abnormal physiological functions of blood cells may be regulated at the level of its receptor. New experimental findings are discussed relating to PDGF receptors in normal leukemic, and virally-infected human cells of myeloid and lymphocytic lineages. At specific developmental stages this regulation may take the form of PDGF and its receptor being expressed or co-expressed; the unmodified or modified form of receptor that specifically interacts with PDGF; the cellular site at which the PDGF-receptor interacts with its ligand; and co-expression of the PDGF-receptor with other receptors associated with specific cell lineage or functions. Elucidation of events involved in synthesis, processing, and interactions of PDGF isoforms and their respective receptors will enable us to develop pharmacological means that may either interfere with, or enhance these desired blood cell functions. This review focuses on PDGF and its receptor in human blood cell differentiation and neoplasia.
Topics: Blood Cells; Cell Differentiation; Deltaretrovirus; Humans; Leukemia; Platelet-Derived Growth Factor; RNA, Messenger; Receptors, Cell Surface; Receptors, Platelet-Derived Growth Factor; T-Lymphocytes
PubMed: 2171978
DOI: 10.1111/j.1600-0609.1990.tb00439.x -
Lab on a Chip Aug 2015We demonstrate the efficient separation of blood cells from millilitre volumes of whole blood in minutes using a simple gravity sedimentation device. Blood cell and...
We demonstrate the efficient separation of blood cells from millilitre volumes of whole blood in minutes using a simple gravity sedimentation device. Blood cell and plasma separation is often the initial step in clinical diagnostics, and reliable separation techniques have remained a major obstacle for the success of point-of-care or remote diagnostics. Unlike plasma collection devices that rely solely on microchannels that restrict sample volume and throughput, we demonstrate the use of a hybrid micro/mesoscale sedimentation chamber to enable >99% capture of cells from millilitre blood samples in less than two minutes.
Topics: Blood Cells; Cell Separation; DNA; Humans; Microfluidic Analytical Techniques; Point-of-Care Systems; Real-Time Polymerase Chain Reaction
PubMed: 26177697
DOI: 10.1039/c5lc00644a -
Medical & Biological Engineering &... Jun 2020In medicine, white blood cells (WBCs) play an important role in the human immune system. The different types of WBC abnormalities are related to different diseases so...
In medicine, white blood cells (WBCs) play an important role in the human immune system. The different types of WBC abnormalities are related to different diseases so that the total number and classification of WBCs are critical for clinical diagnosis and therapy. However, the traditional method of white blood cell classification is to segment the cells, extract features, and then classify them. Such method depends on the good segmentation, and the accuracy is not high. Moreover, the insufficient data or unbalanced samples can cause the low classification accuracy of model by using deep learning in medical diagnosis. To solve these problems, this paper proposes a new blood cell image classification framework which is based on a deep convolutional generative adversarial network (DC-GAN) and a residual neural network (ResNet). In particular, we introduce a new loss function which is improved the discriminative power of the deeply learned features. The experiments show that our model has a good performance on the classification of WBC images, and the accuracy reaches 91.7%. Graphical Abstract Overview of the proposed method, we use the deep convolution generative adversarial networks (DC-GAN) to generate new samples that are used as supplementary input to a ResNet, the transfer learning method is used to initialize the parameters of the network, the output of the DC-GAN and the parameters are applied the final classification network. In particular, we introduced a modified loss function for classification to increase inter-class variations and decrease intra-class differences.
Topics: Blood Cells; Deep Learning; Humans; Image Processing, Computer-Assisted; Leukocytes; Neural Networks, Computer
PubMed: 32221797
DOI: 10.1007/s11517-020-02163-3