Synergistic Integration of Laboratory and Numerical Approaches in Studies of the Biomechanics of Diseased Red Blood Cells

He, Li; Papageorgiou, Dimitrios; Chang, Hung-Yu; Lu, Lu; Yang, Jun; Deng, Yixiang

doi:10.3390/bios8030076

Cited by 17 publications

(14 citation statements)

References 240 publications

(272 reference statements)

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“…It is noted that we did not include other blood cells such as red blood cells in our simulations and thus we cannot consider their interaction with platelets, which could affect platelet transport, particularly in the lumen of the MAs. A more detailed model with explicit representations of the red blood cells and platelets, such as [57][58][59][60][61][62], could be used to explore this effect. See our ongoing work to address this problem in electronic supplementary material, figure S3.…”

Section: Discussionmentioning

confidence: 99%

Predictive modelling of thrombus formation in diabetic retinal microaneurysms

Sampani

Zheng

et al. 2020

R. Soc. open sci.

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Microaneurysms (MAs) are one of the earliest clinically visible signs of diabetic retinopathy (DR). Vision can be reduced at any stage of DR by MAs, which may enlarge, rupture and leak fluid into the neural retina. Recent advances in ophthalmic imaging techniques enable reconstruction of the geometries of MAs and quantification of the corresponding haemodynamic metrics, such as shear rate and wall shear stress, but there is lack of computational models that can predict thrombus formation in individual MAs. In this study, we couple a particle model to a continuum model to simulate the platelet aggregation in MAs with different shapes. Our simulation results show that under a physiologically relevant blood flow rate, thrombosis is more pronounced in saccular-shaped MAs than fusiform-shaped MAs, in agreement with recent clinical findings. Our model predictions of the size and shape of the thrombi in MAs are consistent with experimental observations, suggesting that our model is capable of predicting the formation of thrombus for newly detected MAs. This is the first quantitative study of thrombosis in MAs through simulating platelet aggregation, and our results suggest that computational models can be used to predict initiation and development of intraluminal thrombus in MAs as well as provide insights into their role in the pathophysiology of DR.

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Section: Discussionmentioning

confidence: 99%

Predictive modelling of thrombus formation in diabetic retinal microaneurysms

Sampani

Zheng

et al. 2020

R. Soc. open sci.

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“…Previous studies have shown that five genes (ANK1, SPTB, SPTA1, SLC4A1, and EPB42) encoding red blood cell (RBC) membrane or skeletal proteins are mutated in hereditary spherocytosis [5,6]. A deficiency in or the dysfunction of these proteins results in a reduced surface area-to-volume ratio of spheroidal-shaped red cells due to membrane loss (mostly the intrinsic protein-containing lipid bilayer) and decreased membrane mechanical stability and deformability, which are responsible for the selective trapping of these cells in the spleen [7,8].…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel Mutation of β-Spectrin in Hereditary Spherocytosis Using Whole Exome Sequencing

Bogusławska

Skulski

Machnicka

et al. 2021

IJMS

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Hereditary spherocytosis (HS), the most commonly inherited hemolytic anemia in northern Europeans, comprises a group of diseases whose heterogeneous genetic basis results in a variable clinical presentation. High-throughput genome sequencing methods have made a leading contribution to the recent progress in research on and diagnostics of inherited diseases and inspired us to apply whole exome sequencing (WES) to identify potential mutations in HS. The data presented here reveal a novel mutation probably responsible for HS in a single Polish family. Patients with clinical evidence of HS (clinical symptoms, hematological data, and EMA test) were enrolled in the study. The examination of the resulting WES data showed a number of polymorphisms in 71 genes associated with known erythrocyte pathologies (including membranopathies, enzymopathies, and hemoglobinopathies). Only a single SPTB gene variant indicated the possible molecular mechanism of the disease in the studied family. The new missense mutation p.C183Y was identified using WES in the SPTB gene, which is most likely the cause of clinical symptoms typical of hereditary spherocytosis (membranopathy) due to structural and functional impairments of human β-spectrin. This mutation allows for a better understanding of the molecular mechanism(s) of one of the membranopathies, hereditary spherocytosis.

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“…This multiphysics and multiscale framework was built on a single computational platform (LAMMPS), thereby significantly reducing the computational cost induced by the communication overhead between different solvers. In this work, the authors employ the normal or diabetic RBCs model validated in the previous work of [ 22 , 23 , 71 , 101 , 102 , 103 ].…”

Section: Exacerbated Platelet Aggregation In Diabetic Blood Flowmentioning

confidence: 99%

Recent Advances in Computational Modeling of Biomechanics and Biorheology of Red Blood Cells in Diabetes

Deng

Chang

2022

Biomimetics

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Diabetes mellitus, a metabolic disease characterized by chronically elevated blood glucose levels, affects about 29 million Americans and more than 422 million adults all over the world. Particularly, type 2 diabetes mellitus (T2DM) accounts for 90–95% of the cases of vascular disease and its prevalence is increasing due to the rising obesity rates in modern societies. Although multiple factors associated with diabetes, such as reduced red blood cell (RBC) deformability, enhanced RBC aggregation and adhesion to the endothelium, as well as elevated blood viscosity are thought to contribute to the hemodynamic impairment and vascular occlusion, clinical or experimental studies cannot directly quantify the contributions of these factors to the abnormal hematology in T2DM. Recently, computational modeling has been employed to dissect the impacts of the aberrant biomechanics of diabetic RBCs and their adverse effects on microcirculation. In this review, we summarize the recent advances in the developments and applications of computational models in investigating the abnormal properties of diabetic blood from the cellular level to the vascular level. We expect that this review will motivate and steer the development of new models in this area and shift the attention of the community from conventional laboratory studies to combined experimental and computational investigations, aiming to provide new inspirations for the development of advanced tools to improve our understanding of the pathogenesis and pathology of T2DM.

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Synergistic Integration of Laboratory and Numerical Approaches in Studies of the Biomechanics of Diseased Red Blood Cells

Cited by 17 publications

References 240 publications

Predictive modelling of thrombus formation in diabetic retinal microaneurysms

Predictive modelling of thrombus formation in diabetic retinal microaneurysms

Identification of a Novel Mutation of β-Spectrin in Hereditary Spherocytosis Using Whole Exome Sequencing

Recent Advances in Computational Modeling of Biomechanics and Biorheology of Red Blood Cells in Diabetes

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