Mechanical clearance of red blood cells by the human spleen: Potential therapeutic applications of a biomimetic RBC filtration method

Duez, Julien; Holleran, John; Ndour, Papa Alioune; Pionneau, Cédric; Diakité, Seidina A. S.; Roussel, Camille; Dussiot, Michaël; Amireault, Pascal; Avery, Vicky M.; Buffet, Pierre

doi:10.1016/j.tracli.2015.05.004

Cited by 36 publications

(32 citation statements)

References 46 publications

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“…human spleen perfusion system (15) and in vitro (13,16). The mechanical retention of iRBCs in the spleen is predicted to markedly impact the initial evolution of infection (17,18) and is exploited in the search for new antimalarial drugs (19). Studies of iRBCs and human spleen have further validated the notion that mechanical retention of RBCs is modulated by the spleenspecific 3D structure of the IES in the red pulp (15).…”

Section: Significancementioning

confidence: 99%

Biomechanics of red blood cells in human spleen and consequences for physiology and disease

Pivkin

Peng

Karniadakis

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

203

177

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Red blood cells (RBCs) can be cleared from circulation when alterations in their size, shape, and deformability are detected. This function is modulated by the spleen-specific structure of the interendothelial slit (IES). Here, we present a unique physiological framework for development of prognostic markers in RBC diseases by quantifying biophysical limits for RBCs to pass through the IES, using computational simulations based on dissipative particle dynamics. The results show that the spleen selects RBCs for continued circulation based on their geometry, consistent with prior in vivo observations. A companion analysis provides critical bounds relating surface area and volume for healthy RBCs beyond which the RBCs fail the “physical fitness test” to pass through the IES, supporting independent experiments. Our results suggest that the spleen plays an important role in determining distributions of size and shape of healthy RBCs. Because mechanical retention of infected RBC impacts malaria pathogenesis, we studied key biophysical parameters for RBCs infected with Plasmodium falciparum as they cross the IES. In agreement with experimental results, surface area loss of an infected RBC is found to be a more important determinant of splenic retention than its membrane stiffness. The simulations provide insights into the effects of pressure gradient across the IES on RBC retention. By providing quantitative biophysical limits for RBCs to pass through the IES, the narrowest circulatory bottleneck in the spleen, our results offer a broad approach for developing quantitative markers for diseases such as hereditary spherocytosis, thalassemia, and malaria.

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Section: Significancementioning

confidence: 99%

Biomechanics of red blood cells in human spleen and consequences for physiology and disease

Pivkin

Peng

Karniadakis

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

203

177

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“…In severe malaria caused by P. falciparum or by P. knowlesi the entire red cell population becomes less deformable [ 49 – 52 ]. When red cell deformability was assessed at the shear stresses encountered in the splenic sinusoids (30 Pa) reduced deformability was correlated significantly with the reduction in haemoglobin [ 49 ] (Fig.…”

Section: Pathogenesismentioning

confidence: 99%

Anaemia and malaria

White

2018

Malar J

379

312

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Malaria is a major cause of anaemia in tropical areas. Malaria infection causes haemolysis of infected and uninfected erythrocytes and bone marrow dyserythropoiesis which compromises rapid recovery from anaemia. In areas of high malaria transmission malaria nearly all infants and young children, and many older children and adults have a reduced haemoglobin concentration as a result. In these areas severe life-threatening malarial anaemia requiring blood transfusion in young children is a major cause of hospital admission, particularly during the rainy season months when malaria transmission is highest. In severe malaria, the mortality rises steeply below an admission haemoglobin of 3 g/dL, but it also increases with higher haemoglobin concentrations approaching the normal range. In the management of severe malaria transfusion thresholds remain uncertain. Prevention of malaria by vector control, deployment of insecticide-treated bed nets, prompt and accurate diagnosis of illness and appropriate use of effective anti-malarial drugs substantially reduces the burden of anaemia in tropical countries.

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“…RBCs flow from the perifollicular areas to the lumen of sinuses in the spleen. Alternatively, they also circulate in the splenic red pulp zones upstream of sinuses outside conventional vessels without endothelial lining . Biochemical integrity of RBCs is checked every 2 h (≈1400 times before their clearance).…”

Section: Challenges and Limitations For In Vivo Delivery Of Npsmentioning

confidence: 99%

Biohybrid Nanoparticles to Negotiate with Biological Barriers

Mohammadi

Corbo

Molinaro

et al. 2019

Small

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Incapability of effective cross-talk with biological environments has partly impaired the in vivo functionality of nanoparticles (NPs). Homing, biodistribution, and function of NPs could be engineered through regulating their interactions with in vivo niches. Inspired by communications in biological systems, endowing a "biological identity" to synthetic NPs is one approach to control their biodistribution, and immunonegotiation profiles. This syntheticbiological combination is referred to as biohybrid NPs, which comprise both i) engineerable, readily producible, and trackable synthetic NPs as well as ii) biological moieties with the capability to cross-talk with immunological barriers. Here, the latest understanding on the in vivo interactions of NPs, biological barriers they face, and emerging methods for quantitative measurements of NPs' biodistribution are reviewed. Some key biomolecules that have emerged as negotiators with the immune system in the context of cancer and autoimmunity, and their inspirations on biohybrid NPs are introduced. Critical design considerations for efficient cross-talk between NPs and innate and adaptive immunity followed by hybridization methods are also discussed. Finally, clinical translation challenges and future perspectives regarding biohybrid NPs are discussed.

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Mechanical clearance of red blood cells by the human spleen: Potential therapeutic applications of a biomimetic RBC filtration method

Cited by 36 publications

References 46 publications

Biomechanics of red blood cells in human spleen and consequences for physiology and disease

Biomechanics of red blood cells in human spleen and consequences for physiology and disease

Anaemia and malaria

Biohybrid Nanoparticles to Negotiate with Biological Barriers

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