In silico modeling of patient-specific blood rheology in type 2 diabetes mellitus

Han, Keqin; Ma, Shuhao; Sun, Jiehui; Xu, Miao; Qi, Xiaojing; Wang, Shuo; Li, Li; Li, Xuejin

doi:10.1016/j.bpj.2023.03.010

Cited by 5 publications

(2 citation statements)

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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 [88,89]. DPD can provide the correct hydrodynamic behavior of fluids at the mesoscale, and it has been successfully applied to study complex fluids [90][91][92][93][94][95]. The formulation of the DPD method can be found in S1 Text.…”

Section: Methodsmentioning

confidence: 99%

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

Qiang

et al. 2023

Preprint

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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, there are relatively fewer works on investigating 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 a set of key factors that are 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 five-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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Section: Methodsmentioning

confidence: 99%

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

Qiang

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…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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An In Silico Modelling Approach to Predict Hemodynamic Outcomes in Diabetic and Hypertensive Kidney Disease

Wang,

Benemerito,

Sourbron

et al. 2024

Ann Biomed Eng

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Early diagnosis of kidney disease remains an unmet clinical challenge, preventing timely and effective intervention. Diabetes and hypertension are two main causes of kidney disease, can often appear together, and can only be distinguished by invasive biopsy. In this study, we developed a modelling approach to simulate blood velocity, volumetric flow rate, and pressure wave propagation in arterial networks of ageing, diabetic, and hypertensive virtual populations. The model was validated by comparing our predictions for pressure, volumetric flow rate and waveform-derived indexes with in vivo data on ageing populations from the literature. The model simulated the effects of kidney disease, and was calibrated to align quantitatively with in vivo data on diabetic and hypertensive nephropathy from the literature. Our study identified some potential biomarkers extracted from renal blood flow rate and flow pulsatility. For typical patient age groups, resistive index values were 0.69 (SD 0.05) and 0.74 (SD 0.02) in the early and severe stages of diabetic nephropathy, respectively. Similar trends were observed in the same stages of hypertensive nephropathy, with a range from 0.65 (SD 0.07) to 0.73 (SD 0.05), respectively. Mean renal blood flow rate through a single diseased kidney ranged from 329 (SD 40, early) to 317 (SD 38, severe) ml/min in diabetic nephropathy and 443 (SD 54, early) to 388 (SD 47, severe) ml/min in hypertensive nephropathy, showing potential as a biomarker for early diagnosis of kidney disease. This modelling approach demonstrated its potential application in informing biomarker identification and facilitating the setup of clinical trials.

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In silico modeling of patient-specific blood rheology in type 2 diabetes mellitus

Cited by 5 publications

References 91 publications

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

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

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

An In Silico Modelling Approach to Predict Hemodynamic Outcomes in Diabetic and Hypertensive Kidney Disease

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