Single platelet variability governs population sensitivity and initiates intrinsic heterotypic responses

Jongen, Maaike S. A.; MacArthur, Ben D.; Englyst, Nicola A.; West, Jonathan

doi:10.1038/s42003-020-1002-5

Cited by 8 publications

(5 citation statements)

References 60 publications

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“…74 Again using droplet microfluidics this was shown to be an intrinsic divergence program. 72 However, this still does not explain the zonal distribution of these 2 phenotypes within the thrombus.…”

Section: Intrinsic and Acquired Diversity Of Platelets In Thrombus Fo...mentioning

confidence: 94%

“…Reintroducing paracrine signaling between platelets increased platelet population reactivity 20-fold. 72,73 This implies the presence of hyper-reactive platelets with a pioneer hemostatic function, although this remains speculation without experiments linking such platelets to thrombus initiation. With continued thrombus growth, the phosphatidylserine-exposing platelet polarization phenomena occurs, thus producing proaggregatory and procoagulant states.…”

Section: Platelet Populations In Thrombus Organization and Stabilitymentioning

confidence: 99%

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Emerging Technologies for Understanding Platelet Diversity

West

2022

ATVB

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This review discusses our understanding of platelet diversity with implications for the roles of platelets in hemostasis and thrombosis and identifies advanced technologies set to provide new insights. We use the term diversity to capture intrasubject platelet variability that can be intrinsic or governed by the environment and lead to a heterogeneous response pattern of aggregation, clot promotion, and external communication. Using choice examples, we discuss how the use of advanced technologies can provide new insights into the underlying causes of platelet molecular, structural, and functional diversity. As sources of diversity, we discuss the proliferating megakaryocytes with different allele-specific expression patterns, the asymmetrical formation of proplatelets, changes in platelets induced by aging and priming, interplatelet heterogeneity in thrombus organization and stability, and platelet-dependent communications. We provide indications how current knowledge gaps can be addressed using promising technologies, such as next-generation sequencing, proteomic approaches, advanced imaging techniques, multicolor flow and mass cytometry, multifunctional microfluidics assays, and organ-on-a-chip platforms. We then argue how this technology base can aid in characterizing platelet populations and in identifying platelet biomarkers relevant for the treatment of cardiovascular disease.

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Section: Intrinsic and Acquired Diversity Of Platelets In Thrombus Fo...mentioning

confidence: 94%

Section: Platelet Populations In Thrombus Organization and Stabilitymentioning

confidence: 99%

Emerging Technologies for Understanding Platelet Diversity

West

2022

ATVB

Self Cite

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“…(G) An active micropump mixer with micropump valve chambers and pneumatic actuation chambers from Szydzik et al (2019) . (H) Droplet microfluidics from Jongen et al (2020) ; Top: Schematic of the droplet generator design. Scale bar = 1 mm.…”

Section: Novel Microfluidic Approaches For Platelet Function Assessment and Anti-platelet Drug Screeningmentioning

confidence: 99%

“…Furthermore, Jongen et al (2020) combined droplet microfluidics with flow cytometry for high-throughput single platelet function analysis ( Figure 1H ). The device incorporated four individual inlets to infuse platelets, agonist/antagonist solution and fluoro-oil, which eventually encountered at a common junction where analytes were encapsulated within the fluoro-oil droplets.…”

Section: Novel Microfluidic Approaches For Platelet Function Assessment and Anti-platelet Drug Screeningmentioning

confidence: 99%

Platelet Mechanobiology Inspired Microdevices: From Hematological Function Tests to Disease and Drug Screening

et al. 2022

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Platelet function tests are essential to profile platelet dysfunction and dysregulation in hemostasis and thrombosis. Clinically they provide critical guidance to the patient management and therapeutic evaluation. Recently, the biomechanical effects induced by hemodynamic and contractile forces on platelet functions attracted increasing attention. Unfortunately, the existing platelet function tests on the market do not sufficiently incorporate the topical platelet mechanobiology at play. Besides, they are often expensive and bulky systems that require large sample volumes and long processing time. To this end, numerous novel microfluidic technologies emerge to mimic vascular anatomies, incorporate hemodynamic parameters and recapitulate platelet mechanobiology. These miniaturized and cost-efficient microfluidic devices shed light on high-throughput, rapid and scalable platelet function testing, hematological disorder profiling and antiplatelet drug screening. Moreover, the existing antiplatelet drugs often have suboptimal efficacy while incurring several adverse bleeding side effects on certain individuals. Encouraged by a few microfluidic systems that are successfully commercialized and applied to clinical practices, the microfluidics that incorporate platelet mechanobiology hold great potential as handy, efficient, and inexpensive point-of-care tools for patient monitoring and therapeutic evaluation. Hereby, we first summarize the conventional and commercially available platelet function tests. Then we highlight the recent advances of platelet mechanobiology inspired microfluidic technologies. Last but not least, we discuss their future potential of microfluidics as point-of-care tools for platelet function test and antiplatelet drug screening.

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“…Platelets are small yet highly abundant blood cells that contribute to hemostasis, immunity, and inflammation [1]. Once considered homogeneous, they are now recognized as heterogeneous in size, age, receptor expression, and response to agonist stimulation [2]. While the molecular origins of platelet heterogeneity are unclear, they are likely driven by developmental and environmental factors.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive phenotyping of human platelets by single‐cell cytometry

Spurgeon

Frelinger

2022

Cytometry Pt A

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Platelets are small anucleate blood cells that contribute to hemostasis, immunity, and inflammation. Circulating platelets are heterogeneous in size, age, receptor expression, and reactivity. They inherit many features from megakaryocytes and are further modified on exposure to bioactive substances in the bloodstream. Among these substances, prothrombotic agonists, vasodilators, and bloodborne pathogens modulate platelet phenotypes via distinct signaling cascades. The ability of platelets to respond to (patho)physiologic signals is incompletely understood but likely depends on their repertoire of surface receptors, which may partition them into discrete subsets with specialized functions and divergent abilities. The single-cell resolution of flow and mass cytometry is ideal for immunophenotyping and allows the identification of platelet subsets in remarkable detail. In this report, we describe the surface markers and gating strategies needed for the comprehensive characterization of platelets.

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Single platelet variability governs population sensitivity and initiates intrinsic heterotypic responses

Cited by 8 publications

References 60 publications

Emerging Technologies for Understanding Platelet Diversity

Emerging Technologies for Understanding Platelet Diversity

Platelet Mechanobiology Inspired Microdevices: From Hematological Function Tests to Disease and Drug Screening

Comprehensive phenotyping of human platelets by single‐cell cytometry

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