-
Drug Delivery Dec 2021Brain drug delivery remains a major difficulty for several challenges including the blood-brain barrier, lesion spot targeting, and stability during circulation. Blood...
Brain drug delivery remains a major difficulty for several challenges including the blood-brain barrier, lesion spot targeting, and stability during circulation. Blood cells including erythrocytes, platelets, and various subpopulations of leukocytes have distinct features such as long-circulation, natural targeting, and chemotaxis. The development of biomimetic drug delivery systems based on blood cells for brain drug delivery is growing fast by using living cells, membrane coating nanotechnology, or cell membrane-derived nanovesicles. Blood cell-based vehicles are superior delivery systems for their engineering feasibility and versatile delivery ability of chemicals, proteins, and all kinds of nanoparticles. Here, we focus on advances of blood cell-based biomimetic carriers for from blood to brain drug delivery and discuss their translational challenges in the future.
Topics: Biomimetic Materials; Biomimetics; Blood Cells; Blood-Brain Barrier; Brain Diseases; Drug Carriers; Drug Delivery Systems; Drug Stability; Humans; Nanotechnology
PubMed: 34142628
DOI: 10.1080/10717544.2021.1937384 -
The FEBS Journal Mar 2022Development of multicellular organisms requires the differential usage of our genetic information to change one cell fate into another. This process drives the... (Review)
Review
Development of multicellular organisms requires the differential usage of our genetic information to change one cell fate into another. This process drives the appearance of different cell types that come together to form specialized tissues sustaining a healthy organism. In the last decade, by moving away from studying single genes toward a global view of gene expression control, a revolution has taken place in our understanding of how genes work together and how cells communicate to translate the information encoded in the genome into a body plan. The development of hematopoietic cells has long served as a paradigm of development in general. In this review, we highlight how transcription factors and chromatin components work together to shape the gene regulatory networks controlling gene expression in the hematopoietic system and to drive blood cell differentiation. In addition, we outline how this process goes astray in blood cancers. We also touch upon emerging concepts that place these processes firmly into their associated subnuclear structures adding another layer of the control of differential gene expression.
Topics: Blood Cells; Carcinogenesis; Cell Communication; Cell Differentiation; Cell Lineage; Chromatin; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Hematologic Neoplasms; Hematopoiesis; Hematopoietic Stem Cells; Humans; Neoplasm Proteins; Signal Transduction; Transcription Factors; Transcription, Genetic
PubMed: 33511785
DOI: 10.1111/febs.15735 -
Scientific Reports Nov 2022Treatment of blood smears with Wright's stain is one of the most helpful tools in detecting white blood cell abnormalities. However, to diagnose leukocyte disorders, a...
Treatment of blood smears with Wright's stain is one of the most helpful tools in detecting white blood cell abnormalities. However, to diagnose leukocyte disorders, a clinical pathologist must perform a tedious, manual process of locating and identifying individual cells. Furthermore, the staining procedure requires considerable preparation time and clinical infrastructure, which is incompatible with point-of-care diagnosis. Thus, rapid and automated evaluations of unlabeled blood smears are highly desirable. In this study, we used color spatial light interference microcopy (cSLIM), a highly sensitive quantitative phase imaging (QPI) technique, coupled with deep learning tools, to localize, classify and segment white blood cells (WBCs) in blood smears. The concept of combining QPI label-free data with AI for the purpose of extracting cellular specificity has recently been introduced in the context of fluorescence imaging as phase imaging with computational specificity (PICS). We employed AI models to first translate SLIM images into brightfield micrographs, then ran parallel tasks of locating and labelling cells using EfficientNet, which is an object detection model. Next, WBC binary masks were created using U-net, a convolutional neural network that performs precise segmentation. After training on digitally stained brightfield images of blood smears with WBCs, we achieved a mean average precision of 75% for localizing and classifying neutrophils, eosinophils, lymphocytes, and monocytes, and an average pixel-wise majority-voting F1 score of 80% for determining the cell class from semantic segmentation maps. Therefore, PICS renders and analyzes synthetically stained blood smears rapidly, at a reduced cost of sample preparation, providing quantitative clinical information.
Topics: Neural Networks, Computer; Leukocytes; Microscopy; Lymphocytes; Monocytes
PubMed: 36414631
DOI: 10.1038/s41598-022-21250-z -
Bioengineered Dec 2021Extracellular vesicles (EVs) are released by most of the cells or tissues and act as nanocarriers to transfer nucleic acids, proteins, and lipids. The blood system is...
Extracellular vesicles (EVs) are released by most of the cells or tissues and act as nanocarriers to transfer nucleic acids, proteins, and lipids. The blood system is the most abundant source of extracellular vesicles for purification, and it has attracted considerable attention as a source of diagnostic biomarkers. Blood-derived extracellular vesicles, especially vesicles released from erythrocytes and platelets, are highly important in nanoplatform-based therapeutic interventions as potentially ideal drug delivery vehicles. We reviewed the latest research progress on the paracrine effects and biological functions of extracellular vesicles derived from erythrocytes, leukocytes, platelets, and plasma. From a clinical perspective, we summarize selected useful diagnostic biomarkers for therapeutic intervention and diagnosis. Especially, we describe and discuss the potential application of erythrocyte-derived extracellular vesicles as a new nano-delivery platform for the desired therapeutics. We suggest that blood-derived extracellular vesicles are an ideal nanoplatform for disease diagnosis and therapy.
Topics: Biomarkers; Blood Platelets; Drug Delivery Systems; Early Diagnosis; Erythrocytes; Extracellular Vesicles; Humans
PubMed: 34622717
DOI: 10.1080/21655979.2021.1982320 -
FEBS Letters Dec 2019In vitro cultured blood cells for transfusion purposes provide a safe alternative to donor blood, particularly for patients who require recurrent transfusions, and can... (Review)
Review
In vitro cultured blood cells for transfusion purposes provide a safe alternative to donor blood, particularly for patients who require recurrent transfusions, and can be used as carriers of therapeutic molecules. In vitro derivation of hematopoietic cell types from human-induced pluripotent stem cells (iPSCs) allows for a constant, well-defined production pipeline for such advanced therapeutic and medicinal products. Application of selected iPSC-derived hematopoietic stem cells and hematopoietic effector cells in transplantation/transfusions would avoid the risk of alloimmunization and blood-borne diseases, as well as enable the production of enhanced blood cells expressing molecules that enforce blood cell function or endow novel therapeutic properties. Here, we discuss the state of the art approaches to produce erythroid, megakaryoid and myeloid cells from iPSCs and the biological and technical hurdles that we need to overcome prior to therapeutic application.
Topics: Blood Cells; Blood Donors; Blood Transfusion; Cell Differentiation; Erythroid Cells; Hematopoietic Stem Cells; Humans; Induced Pluripotent Stem Cells; Myeloid Cells; Thrombopoiesis
PubMed: 31520530
DOI: 10.1002/1873-3468.13599 -
BMC Medical Genomics Apr 2024Nonalcoholic fatty liver disease (NAFLD) is on the rise globally, and past research suggests a significant association with various blood cell components. Our goal is to...
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is on the rise globally, and past research suggests a significant association with various blood cell components. Our goal is to explore the potential correlation between whole blood cell indices and NAFLD risk using Mendelian randomization (MR).
METHODS
We analyzed data from 4,198 participants in the 2017-2018 National Health and Nutrition Examination Survey to investigate the link between blood cell indicators and NAFLD. Using various methods like weighted quantile sum and multivariate logistic regression, we assessed the association. Additionally, two-sample Mendelian randomization were employed to infer causality for 36 blood cell indicators and NAFLD.
RESULTS
Multivariate logistic regression identified 10 NAFLD risk factors. Weighted quantile sum revealed a positive correlation (p = 6.03e-07) between total blood cell indices and NAFLD, with hemoglobin and lymphocyte counts as key contributors. Restricted cubic spline analysis found five indicators with significant nonlinear correlations to NAFLD. Mendelian randomization showed a notable association between reticulocyte counts and NAFLD using the inverse-variance weighted method.
CONCLUSIONS
Hematological markers pose an independent NAFLD risk, with a positive causal link found for reticulocyte count. These results emphasize the importance of monitoring NAFLD and investigating specific underlying mechanisms further.
Topics: Humans; Mendelian Randomization Analysis; Non-alcoholic Fatty Liver Disease; Male; Risk Factors; Female; Middle Aged; Blood Cells; Adult; Nutrition Surveys
PubMed: 38654378
DOI: 10.1186/s12920-024-01879-7 -
Molecular Aspects of Medicine Feb 2020Accumulating studies demonstrate that mitochondrial genetics and function are central to determining the susceptibility to, and prognosis of numerous diseases across all... (Review)
Review
Accumulating studies demonstrate that mitochondrial genetics and function are central to determining the susceptibility to, and prognosis of numerous diseases across all organ systems. Despite this recognition, mitochondrial function remains poorly characterized in humans primarily due to the invasiveness of obtaining viable tissue for mitochondrial studies. Recent studies have begun to test the hypothesis that circulating blood cells, which can be obtained by minimally invasive methodology, can be utilized as a biomarker of systemic bioenergetic function in human populations. Here we present the available methodologies for assessing blood cell bioenergetics and review studies that have applied these techniques to healthy and disease populations. We focus on the validation of this methodology in healthy subjects, as well as studies testing whether blood cell bioenergetics are altered in disease, correlate with clinical parameters, and compare with other methodology for assessing human mitochondrial function. Finally, we present the challenges and goals for the development of this emerging approach into a tool for translational research and personalized medicine.
Topics: Biomarkers; Blood Cells; Energy Metabolism; Humans; Mitochondria; Precision Medicine; Translational Research, Biomedical
PubMed: 31864667
DOI: 10.1016/j.mam.2019.100835 -
International Journal of Laboratory... May 2018Morphological review of the peripheral blood smear is still a crucial diagnostic aid as it provides relevant information related to the diagnosis and is important for... (Review)
Review
INTRODUCTION
Morphological review of the peripheral blood smear is still a crucial diagnostic aid as it provides relevant information related to the diagnosis and is important for selection of additional techniques. Nevertheless, the distinctive cytological characteristics of the blood cells are subjective and influenced by the reviewer's interpretation and, because of that, translating subjective morphological examination into objective parameters is a challenge.
METHODS
The use of digital microscopy systems has been extended in the clinical laboratories. As automatic analyzers have some limitations for abnormal or neoplastic cell detection, it is interesting to identify quantitative features through digital image analysis for morphological characteristics of different cells.
RESULT
Three main classes of features are used as follows: geometric, color, and texture. Geometric parameters (nucleus/cytoplasmic ratio, cellular area, nucleus perimeter, cytoplasmic profile, RBC proximity, and others) are familiar to pathologists, as they are related to the visual cell patterns. Different color spaces can be used to investigate the rich amount of information that color may offer to describe abnormal lymphoid or blast cells. Texture is related to spatial patterns of color or intensities, which can be visually detected and quantitatively represented using statistical tools.
CONCLUSION
This study reviews current and new quantitative features, which can contribute to optimize morphology through blood cell digital image processing techniques.
Topics: Blood Cells; Cell Shape; Color; Humans; Image Processing, Computer-Assisted; Microscopy
PubMed: 29741256
DOI: 10.1111/ijlh.12832 -
ELife Dec 2022Piezo1 is the stretch activated Ca channel in red blood cells that mediates homeostatic volume control. Here, we study the organization of Piezo1 in red blood cells...
Piezo1 is the stretch activated Ca channel in red blood cells that mediates homeostatic volume control. Here, we study the organization of Piezo1 in red blood cells using a combination of super-resolution microscopy techniques and electron microscopy. Piezo1 adopts a non-uniform distribution on the red blood cell surface, with a bias toward the biconcave 'dimple'. Trajectories of diffusing Piezo1 molecules, which exhibit confined Brownian diffusion on short timescales and hopping on long timescales, also reflect a bias toward the dimple. This bias can be explained by 'curvature coupling' between the intrinsic curvature of the Piezo dome and the curvature of the red blood cell membrane. Piezo1 does not form clusters with itself, nor does it colocalize with F-actin, Spectrin, or the Gardos channel. Thus, Piezo1 exhibits the properties of a force-through-membrane sensor of curvature and lateral tension in the red blood cell.
Topics: Ion Channels; Erythrocytes; Mechanical Phenomena; Erythrocyte Membrane; Membranes; Mechanotransduction, Cellular
PubMed: 36515266
DOI: 10.7554/eLife.82621 -
Experimental Biology and Medicine... Jun 2021The pathophysiology of sickle cell anemia, a hereditary hemoglobinopathy, has fascinated clinicians and scientists alike since its description over 100 years ago. A... (Review)
Review
The pathophysiology of sickle cell anemia, a hereditary hemoglobinopathy, has fascinated clinicians and scientists alike since its description over 100 years ago. A single gene mutation in the gene results in the production of abnormal hemoglobin (Hb) S, whose polymerization when deoxygenated alters the physiochemical properties of red blood cells, in turn triggering pan-cellular activation and pathological mechanisms that include hemolysis, vaso-occlusion, and ischemia-reperfusion to result in the varied and severe complications of the disease. Now widely regarded as an inflammatory disease, in recent years attention has included the role of leukocytes in vaso-occlusive processes in view of the part that these cells play in innate immune processes, their inherent ability to adhere to the endothelium when activated, and their sheer physical and potentially obstructive size. Here, we consider the role of sickle red blood cell populations in elucidating the importance of adhesion vis-a-vis polymerization in vaso-occlusion, review the direct adhesion of sickle red cells to the endothelium in vaso-occlusive processes, and discuss how red cell- and leukocyte-centered mechanisms are not mutually exclusive. Given the initial clinical success of crizanlizumab, a specific anti-P selectin therapy, we suggest that it is appropriate to take a holistic approach to understanding and exploring the complexity of vaso-occlusive mechanisms and the adhesive roles of the varied cell types, including endothelial cells, platelets, leukocytes, and red blood cells.
Topics: Anemia, Sickle Cell; Animals; Blood Platelets; Cell Adhesion; Erythrocytes; Hemoglobin, Sickle; Humans; Leukocytes; Vascular Diseases
PubMed: 33794696
DOI: 10.1177/15353702211005392