Analysis and prediction of hematocrit in microvascular networks

Li, Guansheng; Ye, Ting; Xia, Zhonghua; Wang, Sitong; Zhu, Ziwei

doi:10.1016/j.ijengsci.2023.103901

Cited by 6 publications

(3 citation statements)

References 67 publications

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“…Literature reports relatively consistent values for kidney, lung, and liver in mice, suggesting that our findings are unlikely to be significantly skewed by these parameters 36,37 . Even if vascular density slightly differed, a linear correlation between blood volume and cell numbers cannot be inferred as the hematocrit (including leukocytes), blood flow and shear stress varies along the complex microvascular vasculature 38,39 . Thus, a direct comparison of different organs is not feasible.…”

Section: Discussionmentioning

confidence: 99%

Microvascular immunity is organ-specific and concealed in peripheral blood

Rixen,

Schütz,

Walter

et al. 2024

Preprint

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Blood tests are a common method for diagnosing and monitoring various health conditions. Nevertheless, the extent to which phlebotomy can offer insights into immune and organ dysfunction remains uncertain. Here, we conducted a comprehensive analysis of blood-borne leukocytes in the microvasculature of different mouse organs and compared it to peripheral blood and parenchymal samples. We observed that microvascular immune cells outnumber tissue-resident counterparts in the kidney, liver and lung. Classical monocytes and lymphocytes are diminished while nonclassical and SSC-high monocytes are enriched compared to blood. Utilizing single-cell sequencing, we identified specific cell populations up to 100-fold expanded in the kidney vasculature including macrophages, plasmacytoid dendritic cells, B cells, and innate lymphoid cells type 2. Microvascular enrichment could trigger a local phenotype switch as shown in glomerulus-restricted B cells. Peritonitis and acute kidney injury (AKI) elicited a multifaceted and systemic response of microvascular leukocytes. It involved remote organ effects, such as a 16-fold increase of leukocytes in the splenic circulation or 64-fold increase of SSC-high monocytes in the liver circulation that was not detectable in the peripheral blood or the tissue. Following full recovery from AKI, persistent and complex changes were observed predominantly in the renal vasculature, while most leukocytes in the peripheral blood had already returned to baseline levels. Collectively, our findings suggest a paradigm of organ- and disease-specific microvascular immunity that largely eludes conventional blood and tissue analysis.

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Section: Discussionmentioning

confidence: 99%

Microvascular immunity is organ-specific and concealed in peripheral blood

Rixen,

Schütz,

Walter

et al. 2024

Preprint

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“…DPD is a mesoscopic particle-based simulation technique, where each DPD particle represents an aggregate of molecules interacting with others through soft pairwise forces [36,37]. This method accurately captures the hydrodynamic behavior of fluids at the mesoscale and has proven successful in investigating complex fluid systems [38,21,39,40]. The evolution of computational capabilities in the past two decades has fostered the advancement and application of multiscale biophysical models for RBCs.…”

Section: Dpd Methods and Multiscale Blood Cell Modelsmentioning

confidence: 99%

Red blood cell passage through deformable interendothelial slits in the spleen: Insights into splenic filtration and hemodynamics

Li,

Ndou

et al. 2024

Preprint

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The spleen constantly clears altered red blood cells (RBCs) from the circulation, tuning the balance between RBC formation (erythropoiesis) and removal. The retention and elimination of RBCs occur predominantly in the open circulation of the spleen, where RBCs must cross submicron-wide inter-endothelial slits (IES). Several experimental and computational studies have illustrated the role of IES in filtrating the biomechanically and morphologically altered RBCs based on a rigid wall assumption. However, these studies also reported that when the size of IES is close to the lower end of clinically observed sizes (less than 0.5μm), an unphysiologically large pressure difference across the IES is required to drive the passage of normal RBCs, sparking debates on the feasibility of the rigid wall assumption. In this work, we perform a computational investigation based on dissipative particle dynamics (DPD) to explore the impact of the deformability of IES on the filtration function of the spleen. We simulate two deformable IES models, namely the passive model and the active model. In the passive model, we implement the worm-like string model to depict the IES’s deformation as it interacts with blood plasma and allows RBC to traverse. In contrast, the active model involved regulating the IES deformation based on the local pressure surrounding the slit. To demonstrate the validity of the deformable model, we simulate the filtration of RBCs with varied size and stiffness by IES under three scenarios: 1) a single RBC traversing a single slit; 2) a suspension of RBCs traversing an array of slits, mimickingin vitrospleen-on-a-chip experiments; 3) RBC suspension passing through the 3D spleen filtration unit known as ‘the splenon’. Our simulation results of RBC passing through a single slit show that the deformable IES model offers more accurate predictions of the critical cell surface area to volume ratio that dictate the removal of aged RBCs from circulation compared to prior rigid-wall models. Our biophysical models of the spleen-on-a-chip indicates a hierarchy of filtration function stringency: rigid model > passive model > active model, providing a possible explanation of why the spleen-on-a-chip could overestimate the filtration function of IES. We also illustrate that the biophysical model of ‘the splenon’ enables us to replicate theex vivoexperiments involving spleen filtration of malaria-infected RBCs. Taken together, our simulation findings indicate that the deformable IES model could serve as a mesoscopic representation of spleen filtration function closer to physiological reality, addressing questions beyond the scope of current experimental and computational models and enhancing our understanding of the fundamental flow dynamics and mechanical clearance processes within in the human spleen.

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“…The DPD method is a mesoscopic particle-based simulation technique, where each DPD particle represents a lump of molecules and interacts with other particles through soft pairwise forces [78]. DPD can provide the correct hydrodynamic behavior of fluids at the mesoscale, and it has been successfully applied to study complex fluids [79][80][81][82]. The formulation of the DPD method can be found in S1 Text.…”

Section: Computational Methods and Modelsmentioning

confidence: 99%

A combined computational and experimental investigation of the filtration function of splenic macrophages in sickle cell disease

Li,

Qiang,

et al. 2023

PLoS Comput Biol

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Being the largest lymphatic organ in the body, the spleen also constantly controls the quality of red blood cells (RBCs) in circulation through its two major filtration components, namely interendothelial slits (IES) and red pulp macrophages. In contrast to the extensive studies in understanding the filtration function of IES, fewer works investigate how the splenic macrophages retain the aged and diseased RBCs, i.e., RBCs in sickle cell disease (SCD). Herein, we perform a computational study informed by companion experiments to quantify the dynamics of RBCs captured and retained by the macrophages. We first calibrate the parameters in the computational model based on microfluidic experimental measurements for sickle RBCs under normoxia and hypoxia, as those parameters are not available in the literature. Next, we quantify the impact of key factors expected to dictate the RBC retention by the macrophages in the spleen, namely, blood flow conditions, RBC aggregation, hematocrit, RBC morphology, and oxygen levels. Our simulation results show that hypoxic conditions could enhance the adhesion between the sickle RBCs and macrophages. This, in turn, increases the retention of RBCs by as much as four-fold, which could be a possible cause of RBC congestion in the spleen of patients with SCD. Our study on the impact of RBC aggregation illustrates a ‘clustering effect’, where multiple RBCs in one aggregate can make contact and adhere to the macrophages, leading to a higher retention rate than that resulting from RBC-macrophage pair interactions. Our simulations of sickle RBCs flowing past macrophages for a range of blood flow velocities indicate that the increased blood velocity could quickly attenuate the function of the red pulp macrophages on detaining aged or diseased RBCs, thereby providing a possible rationale for the slow blood flow in the open circulation of the spleen. Furthermore, we quantify the impact of RBC morphology on their tendency to be retained by the macrophages. We find that the sickle and granular-shaped RBCs are more likely to be filtered by macrophages in the spleen. This finding is consistent with the observation of low percentages of these two forms of sickle RBCs in the blood smear of SCD patients. Taken together, our experimental and simulation results aid in our quantitative understanding of the function of splenic macrophages in retaining the diseased RBCs and provide an opportunity to combine such knowledge with the current knowledge of the interaction between IES and traversing RBCs to apprehend the complete filtration function of the spleen in SCD.

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Analysis and prediction of hematocrit in microvascular networks

Cited by 6 publications

References 67 publications

Microvascular immunity is organ-specific and concealed in peripheral blood

Microvascular immunity is organ-specific and concealed in peripheral blood

Red blood cell passage through deformable interendothelial slits in the spleen: Insights into splenic filtration and hemodynamics

A combined computational and experimental investigation of the filtration function of splenic macrophages in sickle cell disease

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