A novel triple-cell two-dimensional model to study immune-vascular interplay in atherosclerosis

Noonan, J., Grassia, G., MacRitchie, N., Garside, P. , Guzik, T. J., Bradshaw, A. C. and Maffia, P. (2019) A novel triple-cell two-dimensional model to study immune-vascular interplay in atherosclerosis. Frontiers in Immunology, 10, 849. (doi:10.3389/fimmu.2019.00849) (PMID:31068936) (PMCID:PMC6491724)

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Abstract

Atherosclerosis is a complex inflammatory pathology underpinning cardiovascular diseases (CVD), which are the leading cause of death worldwide. The interplay between vascular stromal cells and immune cells is fundamental to the progression and outcome of atherosclerotic disease, however, the majority of in vitro studies do not consider the implications of these interactions and predominantly use mono-culture approaches. Here we present a simple and robust methodology involving the co-culture of vascular endothelial (ECs) and smooth muscle cells (SMCs) alongside an inflammatory compartment, in our study containing THP-1 macrophages, for studying these complex interactions. Using this approach, we demonstrate that the interaction between vascular stromal and immune cells produces unique cellular phenotypes and soluble mediator profiles not observed in double-cell 2D cultures. Our results highlight the importance of cellular communication and support the growing idea that in vitro research must evolve from mono-culture systems to provide data more representative of the multi-cellular environment found in vivo. The methodology presented, in comparison with established approaches, has the advantage of being technically simple whilst enabling the isolation of pure populations of ECs, SMCs and immune cells directly from the co-culture without cell sorting. The approach described within would be applicable to those studying mechanisms of vascular inflammation, particularly in relation to understanding the impact cellular interaction has on the cumulative immune-vascular response to atherogenic or inflammatory stimuli.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Garside, Professor Paul and MacRitchie, Dr Neil and Guzik, Professor Tomasz and Noonan, Dr Jonathan and Maffia, Dr Pasquale and Bradshaw, Dr Angela and Grassia, Dr Gianluca
Authors: Noonan, J., Grassia, G., MacRitchie, N., Garside, P., Guzik, T. J., Bradshaw, A. C., and Maffia, P.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences > Exercise Physiology/Sports Medicine > Clinical Genetics/Genomics
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Frontiers in Immunology
Publisher:Frontiers Media
ISSN:1664-3224
ISSN (Online):1664-3224
Copyright Holders:Copyright © 2019 Noonan, Grassia, MacRitchie, Garside, Guzik, Bradshaw and Maffia
First Published:First published in Frontiers in Immunology 10:849
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
614711Defining innate and adaptive immune functions of plasmacytoid dendritic cells in atherosclerosis.Pasquale MaffiaBritish Heart Foundation (BHF)PG/12/81/29897III -IMMUNOLOGY
617771BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177RI CARDIOVASCULAR & MEDICAL SCIENCES
644661In Situ Nanoparticle Assemblies for Healthcare Diagnostics and TherapyPasquale MaffiaEngineering and Physical Sciences Research Council (EPSRC)EP/L014165/1III -IMMUNOLOGY
682541NanoMATePasquale MaffiaEuropean Commission (EC)661369III -IMMUNOLOGY

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