ArticleProceedings of the National Academy of Sciences of the United States of America2023
Microfluidic study of retention and elimination of abnormal red blood cells by human spleen with implications for sickle cell disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. 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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Who cites it
28 citing papers in PubMed, 49 citations in OpenAlex.
- Shear-Responsive Red Blood Cell Carriers for Targeted Drug Delivery to Constricted Arteries.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Immune Cell Responses to Fluid Shear: Overview and Design Considerations forCurrent opinion in biomedical engineering · 2026Article
- Beyond the mouse: organoids, spheroids, and organs-on-chips as the (inevitable) future of malaria research?Malaria journal · 2026Review
- Deformability-augmented mesenchymal stem cells post-enucleation for efficient mRNA intervention of pulmonary fibrosis in rodent model.iScience · 2026Article
- Microfluidic capillary transit velocity as a functional measure for sickle cell disease andLab on a chip · 2026Article
- Personalized Models of Biological Barriers and Their Diseases: Recent Progress with Organs-On-Chips.Advanced biology · 2026Review
- Splenic Sequestration and Suspected Transient Aplastic Crisis in Sickle-Cell SC/Hemoglobin-G Disease in an Adult: A Case Report.Clinical medicine insights. Case reports · 2026Article
- Microfluidic engineering of immune-competent organs-on-chips and their applications.Frontiers in immunology · 2026Review
- The Immunology of Transfusion Medicine: Past, Present, and Future.Methods in molecular biology (Clifton, N.J.) · 2026Review
- Advances in engineering immune-tumor microenvironments on-a-chip: integrative microfluidic platforms for immunotherapy and drug discovery.Molecular cancer · 2025Review
- Microfluidic Determination of Cell-Derived ATP and Single Cell Pressure Mapping Confirms Benefits of Normoglycemic Stored Red Blood Cells.ACS measurement science au · 2025Article
- Quantifying the unique mechanical properties of irreversibly sickled cells in sickle cell disease.Blood vessels, thrombosis & hemostasis · 2025Article
- Organ-on-chip platforms for nanoparticle toxicity and efficacy assessment: Advancing beyond traditional in vitro and in vivo models.Materials today. Bio · 2025Review
- Sticking together: Polymerization of sickle hemoglobin drives the multiscale pathophysiology of sickle cell disease.Biophysics reviews · 2025Review
- Engineering human immune organoids for translational immunology.Bioactive materials · 2025Review
- Immune organoids: emerging platforms for modeling and analyzing human adaptive immunity.Frontiers in immunology · 2025Review
- An organotypic atlas of human vascular cells.Nature medicine · 2024Article
- Clearance of pathogenic erythrocytes is maintained despite spleen dysfunction in children with sickle cell disease.American journal of hematology · 2024Article
- Red blood cell passage through deformable interendothelial slits in the spleen: Insights into splenic filtration and hemodynamics.Computers in biology and medicine · 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
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
The spleen clears altered red blood cells (RBCs) from circulation, contributing to the balance between RBC formation (erythropoiesis) and removal. The splenic RBC retention and elimination occur predominantly in open circulation where RBCs flow through macrophages and inter-endothelial slits (IESs). The mechanisms underlying and interconnecting these processes significantly impact clinical outcomes. In sickle cell disease (SCD), blockage of intrasplenic sickled RBCs is observed in infants splenectomized due to acute splenic sequestration crisis (ASSC). This life-threatening RBC pooling and organ swelling event is plausibly triggered or enhanced by intra-tissular hypoxia. We present an oxygen-mediated spleen-on-a-chip platform for in vitro investigations of the homeostatic balance in the spleen. To demonstrate and validate the benefits of this general microfluidic platform, we focus on SCD and study the effects of hypoxia on splenic RBC retention and elimination. We observe that RBC retention by IESs and RBC-macrophage adhesion are faster in blood samples from SCD patients than those from healthy subjects. This difference is markedly exacerbated under hypoxia. Moreover, the sickled RBCs under hypoxia show distinctly different phagocytosis processes from those non-sickled RBCs under hypoxia or normoxia. We find that reoxygenation significantly alleviates RBC retention at IESs, and leads to rapid unsickling and fragmentation of the ingested sickled RBCs inside macrophages. These results provide unique mechanistic insights into how the spleen maintains its homeostatic balance between splenic RBC retention and elimination, and shed light on how disruptions in this balance could lead to anemia, splenomegaly, and ASSC in SCD and possible clinical manifestations in other hematologic diseases.
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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.