ArticlePLoS computational biology2021
How the spleen reshapes and retains young and old red blood cells: A computational investigation.
Article in PLoS computational biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- Erythrocyte Glycolytic and Redox Metabolism Affects Muscle Oxygenation and Exercise Performance: A Randomized Double-Blind Crossover Study in Men.Sports medicine (Auckland, N.Z.) · 2025Trial
- Shear-Responsive Red Blood Cell Carriers for Targeted Drug Delivery to Constricted Arteries.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Deciphering the association between Sirt2 modulation and non-canonical Wnt/planar cell polarity-dependent splenic junctional priming: a comparative study of two Sirt2 modulators in murine endotoxemia.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- In Silico Post-screening of Anti-polymerization Agents to Treat Sickle Cell Disease.bioRxiv : the preprint server for biology · 2025Article
- Stomatocyte-discocyte-echinocyte transformations of erythrocyte modulated by membrane-cytoskeleton mechanical properties.Biophysical journal · 2025Article
- Uniform impact on individual megakaryocytes is essential for efficient in vitro platelet production.Scientific reports · 2025Article
- Ergosterone ameliorates RRR-induced spleen deficiency by gut microbiota-gut metabolites and P38MAPK signaling pathway.Frontiers in microbiology · 2025Article
- Clearance of pathogenic erythrocytes is maintained despite spleen dysfunction in children with sickle cell disease.American journal of hematology · 2024Article
- The dynamics of red blood cells traversing slits of mechanical heart valves under high shear.Biophysical journal · 2024Article
- Biomechanics of phagocytosis of red blood cells by macrophages in the human spleen.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Lysis of human erythrocytes due to Piezo1-dependent cytosolic calcium overload as a mechanism of circulatory removal.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Efficient and highly reproducible production of red blood cell-derived extracellular vesicle mimetics for the loading and delivery of RNA molecules.Scientific reports · 2024Article
- Biomechanics of circulating cellular and subcellular bioparticles: beyond separation.Cell communication and signaling : CCS · 2024Review
- Artificial cells for in vivo biomedical applications through red blood cell biomimicry.Nature communications · 2024Review
- Signaling-biophysical modeling unravels mechanistic control of red blood cell phagocytosis by macrophages in sickle cell disease.PNAS nexus · 2024Article
- A combined computational and experimental investigation of the filtration function of splenic macrophages in sickle cell disease.PLoS computational biology · 2023Article
- In silico and in vitro study of the adhesion dynamics of erythrophagocytosis in sickle cell disease.Biophysical journal · 2023Article
- Article
- Evolution of surface area and membrane shear modulus of matured human red blood cells during mechanical fatigue.Scientific reports · 2023Article
- In silico modeling of patient-specific blood rheology in type 2 diabetes mellitus.Biophysical journal · 2023Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The spleen, the largest secondary lymphoid organ in humans, not only fulfils a broad range of immune functions, but also plays an important role in red blood cell's (RBC) life cycle. Although much progress has been made to elucidate the critical biological processes involved in the maturation of young RBCs (reticulocytes) as well as removal of senescent RBCs in the spleen, the underlying mechanisms driving these processes are still obscure. Herein, we perform a computational study to simulate the passage of RBCs through interendothelial slits (IES) in the spleen at different stages of their lifespan and investigate the role of the spleen in facilitating the maturation of reticulocytes and in clearing the senescent RBCs. Our simulations reveal that at the beginning of the RBC life cycle, intracellular non-deformable particles in reticulocytes can be biomechanically expelled from the cell upon passage through IES, an insightful explanation of why this peculiar "pitting" process is spleen-specific. Our results also show that immature RBCs shed surface area by releasing vesicles after crossing IES and progressively acquire the biconcave shape of mature RBCs. These findings likely explain why RBCs from splenectomized patients are significantly larger than those from nonsplenectomized subjects. Finally, we show that at the end of their life span, senescent RBCs are not only retained by IES due to reduced deformability but also become susceptible to mechanical lysis under shear stress. This finding supports the recent hypothesis that transformation into a hemolyzed ghost is a prerequisite for phagocytosis of senescent RBCs. Altogether, our computational investigation illustrates critical biological processes in the spleen that cannot be observed in vivo or in vitro and offer insights into the role of the spleen in the RBC physiology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.