Developing a xenograft model of human vasculature in the mouse ear pinna

Meehan, G. R. , Scales, H. E. , Osii, R., De Niz, M., Lawton, J. C., Marti, M. , Garside, P. , Craig, A. and Brewer, J. M. (2020) Developing a xenograft model of human vasculature in the mouse ear pinna. Scientific Reports, 10, 2058. (doi: 10.1038/s41598-020-58650-y) (PMID:32029768) (PMCID:PMC7004987)

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Abstract

Humanised xenograft models allow for the analysis of human tissue within a physiological environment in vivo. However, current models often rely on the angiogenesis and ingrowth of recipient vasculature to perfuse tissues, preventing analysis of biological processes and diseases involving human blood vessels. This limits the effectiveness of xenografts in replicating human physiology and may lead to issues with translating findings into human research. We have designed a xenograft model of human vasculature to address this issue. Human subcutaneous fat was cultured in vitro to promote blood vessel outgrowth prior to implantation into immunocompromised mice. We demonstrate that implants survived, retained human vasculature and anastomosed with the circulatory system of the recipient mouse. Significantly, by performing transplants into the ear pinna, this system enabled intravital observation of xenografts by multiphoton microscopy, allowing us to visualise the steps leading to vascular cytoadherence of erythrocytes infected with the human parasite Plasmodium falciparum. This model represents a useful tool for imaging the interactions that occur within human tissues in vivo and permits visualization of blood flow and cellular recruitment in a system which is amenable to intervention for various studies in basic biology together with drug evaluation and mechanism of action studies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Marti, Professor Matthias and Garside, Professor Paul and Brewer, Professor James and Osii, Rowland and Scales, Dr Hannah and Meehan, Dr Gavin and Lawton, Dr Jennifer and De Niz, Dr Mariana
Authors: Meehan, G. R., Scales, H. E., Osii, R., De Niz, M., Lawton, J. C., Marti, M., Garside, P., Craig, A., and Brewer, J. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Scientific Reports
Publisher:Nature Research
ISSN:2045-2322
ISSN (Online):2045-2322
Copyright Holders:Copyright © 2020 The Authors
First Published:First published in Scientific Reports 10: 2058
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
166225Cytoadherence-mediated pathology in cerebral malariaJames BrewerWellcome Trust (WELLCOTR)095507/Z/11/ZIII - Immunology