Magnetic Accumulation of SPIONs under Arterial Flow Conditions: Effect of Serum and Red Blood Cells

Magnetic drug targeting utilizes an external magnetic field to target superparamagnetic iron oxide nanoparticles (SPIONs) and their cargo to the diseased vasculature regions. In the arteries, the flow conditions affect the behavior of magnetic particles and the efficacy of their accumulation. In order to estimate the magnetic capture of SPIONs in more physiological-like settings, we previously established an ex vivo model based on human umbilical cord arteries. The artery model was employed in our present studies in order to analyze the effects of the blood components on the efficacy of magnetic targeting, utilizing 2 types of SPIONs with different physicochemical characteristics. In the presence of freshly isolated human plasma or whole blood, a strong increase in iron content measured by AES was observed for both particle types along the artery wall, in parallel with clotting activation due to endogenous thrombin generation in plasma. Subsequent studies therefore utilized SPION suspensions in serum and washed red blood cells (RBCs) at hematocrit 50%. Interestingly, in contrast to cell culture medium suspensions, magnetic accumulation of circulating SPION-3 under the external magnet was achieved in the presence of RBCs. Taken together, our data shows that the presence of blood components affects, but does not prevent, the magnetic accumulation of circulating SPIONs.

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Abstract 3680: Transfusion-Induced Tissue Hypoxia is Ameliorated by S -nitrosohemoglobin Repletion of Stored Red Blood Cells

Circulation ◽

10.1161/circ.118.suppl_18.s_465-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Diana L Diesen ◽

Jonathan S Stamler

Keyword(s):

Animal Models ◽

Red Blood Cells ◽

Blood Cells ◽

Tissue Oxygenation ◽

Ex Vivo ◽

Tissue Hypoxia ◽

Mouse Blood ◽

Mortality And Morbidity ◽

Stored Blood ◽

Related Mortality

Transfusion of stored red blood cells (RBCs) is associated with a decrease in tissue oxygenation in animal models and with increased mortality and morbidity in patients. Recent studies have demonstrated that stored RBCs are deficient in vasodilatory ability and depleted of S -nitrosohemoglobin (SNO-Hb), and that renitrosylation ex vivo can increase SNO-Hb levels and restore vasoactivity. We have examined in a mouse model the extent to which transfusion impairs tissue oxygenation and whether SNO-Hb repletion can ameliorate that impairment. We report here that transfusion of (mouse) RBCs stored for 1 day or 1 week results in tissue hypoxia that is largely prevented by SNO-Hb repletion prior to transfusion ( 1 day stored blood : % decrease in oxygenation 58+/−10% untreated vs. 92+/−0.7% SNO-Hb repleted, p<0.05, n=3– 6; 1 week stored blood : % decrease in oxygenation 66+/−10% untreated vs. 91+/−2.8% SNO-Hb repleted, p<0.05, n=3– 6). Storage of mouse blood beyond human expiration-equivalents (1 month) resulted in substantial lysis and the death of all mice transfused (native and SNO-Hb repleted blood, n=5). In conclusion, repletion of SNO-Hb ameliorates the decrease in tissue oxygenation that results from transfusion of untreated stored blood. Therefore, SNO-Hb repletion may provide a simple and efficacious method to reduce transfusion-related mortality and morbidity.

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More efficient exchange of sickle red blood cells can be achieved by exchanging the densest red blood cells: An ex vivo proof of concept study

Transfusion and Apheresis Science ◽

10.1016/j.transci.2018.12.005 ◽

2019 ◽

Vol 58 (1) ◽

pp. 100-106

Author(s):

Suzanne R. Thibodeaux ◽

Yvette C. Tanhehco ◽

Leah Irwin ◽

Lita Jamensky ◽

Kevin Schell ◽

...

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Ex Vivo ◽

Proof Of Concept ◽

Concept Study ◽

Sickle Red Blood Cells

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Sensing of red blood cells with decreased membrane deformability by the human spleen

Blood Advances ◽

10.1182/bloodadvances.2018024562 ◽

2018 ◽

Vol 2 (20) ◽

pp. 2581-2587 ◽

Cited By ~ 11

Author(s):

Innocent Safeukui ◽

Pierre A. Buffet ◽

Guillaume Deplaine ◽

Sylvie Perrot ◽

Valentine Brousse ◽

...

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Ex Vivo ◽

Volume Ratio ◽

Red Cells ◽

Human Spleen ◽

Rbc Membrane ◽

Membrane Rigidity ◽

Cellular Deformability ◽

Distinct Features

Abstract The current paradigm in the pathogenesis of several hemolytic red blood cell disorders is that reduced cellular deformability is a key determinant of splenic sequestration of affected red cells. Three distinct features regulate cellular deformability: membrane deformability, surface area-to-volume ratio (cell sphericity), and cytoplasmic viscosity. By perfusing normal human spleens ex vivo, we had previously showed that red cells with increased sphericity are rapidly sequestered by the spleen. Here, we assessed the retention kinetics of red cells with decreased membrane deformability but without marked shape changes. A controlled decrease in membrane deformability (increased membrane rigidity) was induced by treating normal red cells with increasing concentrations of diamide. Following perfusion, diamide-treated red blood cells (RBCs) were rapidly retained in the spleen with a mean clearance half-time of 5.9 minutes (range, 4.0-13.0). Splenic clearance correlated positively with increased membrane rigidity (r = 0.93; P < .0001). To determine to what extent this increased retention was related to mechanical blockade in the spleen, diamide-treated red cells were filtered through microsphere layers that mimic the mechanical sensing of red cells by the spleen. Diamide-treated red cells were retained in the microsphilters (median, 7.5%; range, 0%-38.6%), although to a lesser extent compared with the spleen (median, 44.1%; range, 7.3%-64.0%; P < .0001). Taken together, these results have implications for understanding the sensitivity of the human spleen to sequester red cells with altered cellular deformability due to various cellular alterations and for explaining clinical heterogeneity of RBC membrane disorders.

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Erythroblast Enucleation

Stem Cells International ◽

10.4061/2011/139851 ◽

2011 ◽

Vol 2011 ◽

pp. 1-9 ◽

Cited By ~ 55

Author(s):

Ganesan Keerthivasan ◽

Amittha Wickrema ◽

John D. Crispino

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Ex Vivo ◽

Critical Rate ◽

Future Directions ◽

Mammalian Erythrocyte ◽

Rate Limiting

Even though the production of orthochromatic erythroblasts can be scaled up to fulfill clinical requirements, enucleation remains one of the critical rate-limiting steps in the production of transfusable red blood cells. Mammalian erythrocytes extrude their nucleus prior to entering circulation, likely to impart flexibility and improve the ability to traverse through capillaries that are half the size of erythrocytes. Recently, there have been many advances in our understanding of the mechanisms underlying mammalian erythrocyte enucleation. This review summarizes these advances, discusses the possible future directions in the field, and evaluates the prospects for improved ex vivo production of red blood cells.

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Storage-related changes in autologous whole blood and irradiated allogeneic red blood cells and their ex vivo effects on deformability, indices, and density of circulating erythrocytes in patients undergoing cardiac surgery with cardiopulmonary bypass

Journal of Cardiothoracic and Vascular Anesthesia ◽

10.1053/j.jvca.2021.06.016 ◽

2021 ◽

Author(s):

Junko Ichikawa ◽

Ichiro Koshino ◽

Nobuto Arashiki ◽

Fumio Nakamura ◽

Makiko Komori

Keyword(s):

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Red Blood Cells ◽

Whole Blood ◽

Blood Cells ◽

Ex Vivo ◽

Autologous Whole Blood

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Ex vivo generation of transfusable red blood cells from various stem cell sources: A concise revisit of where we are now

Transfusion and Apheresis Science ◽

10.1016/j.transci.2018.12.015 ◽

2019 ◽

Vol 58 (1) ◽

pp. 108-112 ◽

Cited By ~ 10

Author(s):

Evangelia-Eleni Christaki ◽

Marianna Politou ◽

Marianna Antonelou ◽

Angelos Athanasopoulos ◽

Emmanouil Simantirakis ◽

...

Keyword(s):

Stem Cell ◽

Red Blood Cells ◽

Blood Cells ◽

Ex Vivo ◽

Cell Sources

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Human erythroid cells produced ex vivo at large scale differentiate into red blood cells in vivo

Nature Biotechnology ◽

10.1038/nbt0502-467 ◽

2002 ◽

Vol 20 (5) ◽

pp. 467-472 ◽

Cited By ~ 186

Author(s):

Thi My Anh Neildez-Nguyen ◽

Henri Wajcman ◽

Michael C. Marden ◽

Morad Bensidhoum ◽

Vincent Moncollin ◽

...

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Large Scale ◽

Ex Vivo ◽

Erythroid Cells

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INTERPRETATION OF THE RESULTS OF IMMUNOHEMATOLOGICAL TESTS IN HEMATOLOGICAL PATIENTS

Russian Clinical Laboratory Diagnostics ◽

10.18821/0869-2084-2019-64-4-221-224 ◽

2019 ◽

Vol 64 (4) ◽

pp. 221-224

Author(s):

A. V. Yovdiy ◽

E. V. Butina ◽

E. A. Poponina ◽

G. A. Zaitseva ◽

N. V. Minaeva

Keyword(s):

Red Blood Cells ◽

Blood Cells ◽

Blood Components ◽

Blood Types ◽

Hematological Patients ◽

Correct Determination ◽

Double Population ◽

Transfusion Complications ◽

Selection Of

The correct determination of the blood types of the recipient and the donor is very importante for the choice of blood components for transfusion. As a result of the study, it was established that 18.0% of patients, admitted to the hematology clinic, have difficulties in interpreting of the results of immunohematological tests. Most often, a double population of red blood cells was detected when determining antigens of the Rhesus system (10.9%), auto- (3.9%) and alloantibodies (2.8%). The proposed algorithm for the selection of donor red blood cells in difficult diagnostic cases helps to prevent the development of post-transfusion complications.

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