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Surgery Dec 2022Current management of hemorrhagic shock relies on control of surgical bleeding along with resuscitation with packed red blood cells and plasma in a 1-to-1 ratio....
BACKGROUND
Current management of hemorrhagic shock relies on control of surgical bleeding along with resuscitation with packed red blood cells and plasma in a 1-to-1 ratio. Transfusion, however, is not without consequence as red blood cells develop a series of biochemical and physical changes during storage termed "the red blood cell storage lesion." Previous data has suggested that ethanol may stabilize the red blood cell membrane, resulting in improved deformability. We hypothesized that storage of packed red blood cells with ethanol would alter the red blood cell storage lesion.
METHODS
Mice underwent donation and storage of red blood cells with standard storage conditions in AS-3 alone or ethanol at concentrations of 0.07%, 0.14%, and 0.28%. The red blood cell storage lesion parameters of microvesicles, Band-3, free hemoglobin, annexin V, and erythrocyte osmotic fragility were measured and compared. In additional experiments, the mice underwent hemorrhage and resuscitation with stored packed red blood cells to further evaluate the in vivo inflammatory impact.
RESULTS
Red blood cells stored with ethanol demonstrated decreased microvesicle accumulation and Band-3 levels. There were no differences in phosphatidylserine or cell-free hemoglobin levels. After hemorrhage and resuscitation with packed red blood cells stored with 0.07% ethanol, mice demonstrated decreased serum levels of interleukin-6, macrophage inflammatory protein-1α, keratinocyte chemokine, and tumor necrosis factor α compared to those mice receiving packed red blood cells stored with additive solution-3.
CONCLUSION
Storage of murine red blood cells with low-dose ethanol results in decreased red blood cell storage lesion severity. Resuscitation with packed red blood cells stored with 0.07% ethanol also resulted in a decreased systemic inflammatory response in a murine model of hemorrhage.
Topics: Mice; Animals; Erythrocyte Transfusion; Ethanol; Erythrocytes; Hemoglobins; Hemorrhage
PubMed: 36109200
DOI: 10.1016/j.surg.2022.07.016 -
Experimental Hematology Oct 2016Allogeneic hematopoietic stem cell transplantation and blood cell transfusions are performed commonly in patients with a variety of blood disorders. Unfortunately, these... (Review)
Review
Allogeneic hematopoietic stem cell transplantation and blood cell transfusions are performed commonly in patients with a variety of blood disorders. Unfortunately, these donor-derived cell therapies are constrained due to limited supplies, infectious risk factors, a lack of appropriately matched donors, and the risk of immunologic complications from such products. The use of autologous cell therapies has been proposed to overcome these shortcomings. One can derive such therapies directly from hematopoietic stem and progenitor cells of individuals, which can then be manipulated ex vivo to produce the desired modifications or differentiated to produce a particular target population. Alternatively, pluripotent stem cells, which have a theoretically unlimited self-renewal capacity and an ability to differentiate into any desired cell type, can be used as an autologous starting source for such manipulation and differentiation approaches. Such cell products can also be used as a delivery vehicle for therapeutics. In this review, we highlight recent advances and discuss ongoing challenges for the in vitro generation of autologous hematopoietic cells that can be used for cell therapy.
Topics: Animals; Blood Cells; Blood Transfusion, Autologous; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cell- and Tissue-Based Therapy; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Transplantation, Autologous
PubMed: 27345108
DOI: 10.1016/j.exphem.2016.06.005 -
Frontiers in Cellular and Infection... 2022Parasites of the genus that cause malaria survive within humans by invasion of, and proliferation within, the most abundant cell type in the body, the red blood cell.... (Review)
Review
Parasites of the genus that cause malaria survive within humans by invasion of, and proliferation within, the most abundant cell type in the body, the red blood cell. As obligate, intracellular parasites, interactions between parasite and host red blood cell components are crucial to multiple aspects of the blood stage malaria parasite lifecycle. The requirement for, and involvement of, an array of red blood cell proteins in parasite invasion and intracellular development is well established. Nevertheless, detailed mechanistic understanding of host cell protein contributions to these processes are hampered by the genetic intractability of the anucleate red blood cell. The advent of stem cell technology and more specifically development of methods that recapitulate the process of red blood cell development known as erythropoiesis has enabled the generation of erythroid cell stages previously inaccessible in large numbers for malaria studies. What is more, the capacity for genetic manipulation of nucleated erythroid precursors that can be differentiated to generate modified red blood cells has opened new horizons for malaria research. This review summarises current methodologies that harness erythroid differentiation of stem cells for generation of cells that are susceptible to malaria parasite invasion; discusses existing and emerging approaches to generate novel red blood cell phenotypes and explores the exciting potential of derived red blood cells for improved understanding the broad role of host red blood cell proteins in malaria pathogenesis.
Topics: Humans; Erythrocytes; Malaria; Stem Cells; Erythropoiesis; Cell Differentiation
PubMed: 36452302
DOI: 10.3389/fcimb.2022.1039520 -
Stem Cells Translational Medicine Nov 2021Red blood cells (RBCs) and platelets derived from stem cells are possible solutions to the increasing demand for blood transfusion. Based on the availability of stem... (Review)
Review
Red blood cells (RBCs) and platelets derived from stem cells are possible solutions to the increasing demand for blood transfusion. Based on the availability of stem cells, their relatively defined differentiation mechanisms, and the massive exploration of induction systems, the generation of RBCs or platelets in vitro from cord blood hematopoietic stem/progenitor cells (CB-HSPCs) has potential for clinical applications. However, information on the clinical translation of stem cell-derived RBCs and platelets in the literature and at the ClinicalTrials.gov website is very limited. The only clinical trial on cultured RBCs, which aimed to assess the lifespan of RBCs cultured in vivo, was reported by Luc Douay and colleagues. Of note, the cultured RBCs they used were derived from autologous peripheral blood HSPCs, and no cultured platelets have been applied clinically to date. However, CB-HSPC-derived megakaryocytes, platelet precursors, have been used in the treatment of thrombocytopenia. A successful phase I trial was reported, followed by phase II and III clinical trials conducted in China. In this review, the gap between the many basic studies and limited clinical trials on stem cell-derived RBCs and platelets is summarized. The possible reasons and solutions for this gap are discussed. Further technological improvements for blood cell expansion and maturation ex vivo and the establishment of biological standards for stem cell derivatives might help to facilitate the therapeutic applications of cultured RBCs and platelets derived from CB-HSPCs in the near future.
Topics: Antigens, CD34; Blood Platelets; Cell Differentiation; Cells, Cultured; Erythrocytes; Fetal Blood; Hematopoietic Stem Cells; Humans; Megakaryocytes
PubMed: 34724719
DOI: 10.1002/sctm.20-0517 -
Stem Cells Translational Medicine Mar 2014Blood transfusion is a common procedure in modern medicine, and it is practiced throughout the world; however, many countries report a less than sufficient blood supply.... (Review)
Review
Blood transfusion is a common procedure in modern medicine, and it is practiced throughout the world; however, many countries report a less than sufficient blood supply. Even in developed countries where the supply is currently adequate, projected demographics predict an insufficient supply as early as 2050. The blood supply is also strained during occasional widespread disasters and crises. Transfusion of blood components such as red blood cells (RBCs), platelets, or neutrophils is increasingly used from the same blood unit for multiple purposes and to reduce alloimmune responses. Even for RBCs and platelets lacking nuclei and many antigenic cell-surface molecules, alloimmunity could occur, especially in patients with chronic transfusion requirements. Once alloimmunization occurs, such patients require RBCs from donors with a different blood group antigen combination, making it a challenge to find donors after every successive episode of alloimmunization. Alternative blood substitutes such as synthetic oxygen carriers have so far proven unsuccessful. In this review, we focus on current research and technologies that permit RBC production ex vivo from hematopoietic stem cells, pluripotent stem cells, and immortalized erythroid precursors.
Topics: Antigens, CD; Biomarkers; Blood Transfusion; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cell Separation; Erythrocytes; Erythropoiesis; Feeder Cells; Hematopoietic Stem Cells; Humans; Isoantigens; Pluripotent Stem Cells; Reticulocytes
PubMed: 24361925
DOI: 10.5966/sctm.2013-0054 -
Haematologica Aug 2022
Topics: Blood Cells; Bone Marrow; Diagnosis, Differential; Histiocytic Necrotizing Lymphadenitis; Humans; Lymph Nodes
PubMed: 35484646
DOI: 10.3324/haematol.2022.280746 -
Folia Neuropathologica 2018In elderly population, Alzheimer's disease is a common neurodegenerative disorder and accounts for about 70% of all cases of dementia. The neurodegenerative processes of... (Review)
Review
In elderly population, Alzheimer's disease is a common neurodegenerative disorder and accounts for about 70% of all cases of dementia. The neurodegenerative processes of this disease start presumably 20 years ahead of the clinical beginning of the disorder. The postmortem histopathological examination, brains from Alzheimer's disease patients with characteristic features like amyloid plaques and neurofibrillary tangles, neuronal and synaptic disintegration confirm the final diagnosis of Alzheimer's disease. Senile plaques are composed of -amyloid peptide, deriving from the amyloid protein precursor, which is present not only in the brain tissue, but also in other non-neuronal tissues. Some investigations reported that platelets possess amyloid protein precursor and all the enzymatic activities required for the metabolism of this protein throughout the same pathways present in the brain. Thus, platelets may be a good peripheral blood cell-based biomarker to study the onset of Alzheimer's disease. Another line of research indicated molecular and cellular aberrations in blood lymphocytes and erythrocytes from Alzheimer's disease patients and emphasizes the systemic nature of the disease. In this review, we will summarize the recent knowledge on the involvement and/or response of platelets, lymphocytes and red blood cells in the circulation during Alzheimer's disease development. The facts will be reviewed with the special possibility for applying the above blood cells as Alzheimer's disease preclinical and antemortem blood cell-based biomarkers.
Topics: Alzheimer Disease; Biomarkers; Blood Platelets; Erythrocytes; Humans; Lymphocytes
PubMed: 29663736
DOI: 10.5114/fn.2018.74655 -
Blood Cells, Molecules & Diseases Mar 2021While red blood cells (RBCs) and granulocytes have been more studied, platelets and reticulocytes are not commonly used in paroxysmal nocturnal hemoglobinuria (PNH)...
While red blood cells (RBCs) and granulocytes have been more studied, platelets and reticulocytes are not commonly used in paroxysmal nocturnal hemoglobinuria (PNH) flow-cytometry and less is known about susceptibility to complement-mediated destruction and effects of anti-complement therapy on these populations. We performed flow-cytometry of RBCs and granulocytes in 90 PNH patients and of platelets and reticulocytes in a subgroup (N = 36), to unveil perturbations of these populations during PNH disease course before and after anti-complement treatment. We found that platelets and reticulocytes were less sensitive to complement-mediated lysis than RBCs but not as resistant as granulocytes, as shown by mean sensitive fraction (difference in a given PNH population vs. PNH granulocyte clone size). In treated patients, reticulocytes, platelets, RBCs (with differences between type II and III) and granulocytes significantly increased post-treatment, confirming the role of PNH hematopoiesis within the context of anti-complement therapy. Moreover, we found that PNH platelet clone size reflects PNH granulocyte clone size. Finally, we established correlations between sensitive fraction of PNH cell-types and thrombosis. In sum, we applied a flow-cytometry panel for investigation of PNH peripheral blood populations' perturbations before and after eculizumab treatment to explore complement-sensitivity and kinetics of these cells during the disease course.
Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Blood Cells; Blood Platelets; Complement Inactivating Agents; Erythrocytes; Erythroid Cells; Female; Flow Cytometry; Granulocytes; Hemoglobinuria, Paroxysmal; Humans; Male; Middle Aged; Reticulocytes; Young Adult
PubMed: 33341510
DOI: 10.1016/j.bcmd.2020.102528 -
Environmental Research Mar 2022It has been hypothesized that solar and geomagnetic activity can affect the function of the autonomic nervous system (ANS) and melatonin secretion, both of which may...
It has been hypothesized that solar and geomagnetic activity can affect the function of the autonomic nervous system (ANS) and melatonin secretion, both of which may influence immune response. We investigated the association between solar geomagnetic activity and white blood cell counts in the Normative Aging Study (NAS) Cohort between 2000 and 2013. Linear mixed effects models with moving day averages ranging from 0 to 28 days were used to evaluate the effects of solar activity measures, interplanetary magnetic field (IMF), and sunspot number (SSN), and a measure of geomagnetic activity, K Index (K), on total white blood cell (WBC), neutrophil, monocytes, lymphocyte, eosinophil, and basophil concentrations. After adjusting for demographic and health-related factors, there were consistently significant associations between IMF, SSN, and K index, with reductions in total WBC, neutrophils, and basophil counts. These associations were stronger with longer moving averages. The associations were similar after adjusting for ambient air particulate pollution and particle radioactivity. Our findings suggest that periods of increased solar and geomagnetic activity result in lower WBC, neutrophil, and basophil counts that may contribute to mil mild immune suppression.
Topics: Aging; Humans; Leukocyte Count; Leukocytes; Monocytes; Neutrophils
PubMed: 34537201
DOI: 10.1016/j.envres.2021.112066 -
International Journal of Molecular... Apr 2021While differences among donors has long challenged meeting quality standards for the production of blood components for transfusion, only recently has the molecular... (Review)
Review
While differences among donors has long challenged meeting quality standards for the production of blood components for transfusion, only recently has the molecular basis for many of these differences become understood. This review article will examine our current understanding of the molecular differences that impact the quality of red blood cells (RBC), platelets, and plasma components. Factors affecting RBC quality include cytoskeletal elements and membrane proteins associated with the oxidative response as well as known enzyme polymorphisms and hemoglobin variants. Donor age and health status may also be important. Platelet quality is impacted by variables that are less well understood, but that include platelet storage sensitive metabolic parameters, responsiveness to agonists accumulating in storage containers and factors affecting the maintenance of pH. An increased understanding of these variables can be used to improve the quality of blood components for transfusion by using donor management algorithms based on a donors individual molecular and genetic profile.
Topics: Age Factors; Blood Donors; Blood Platelets; Blood Preservation; Erythrocytes; Humans
PubMed: 33920459
DOI: 10.3390/ijms22083943