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

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Meehan,, Gavin R., Scales,, Hannah E., Osii,, Rowland, De Niz,, Mariana, Lawton, Jennifer C., Marti,, Matthias, Garside,, Paul, Craig, Alister ORCID: https://orcid.org/0000-0003-0914-6164 and Brewer, James M. (2020) 'Developing a xenograft model of human vasculature in the mouse ear pinna'. Scientific Reports, Vol 10, p. 2058.

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Alister Craig789537v1.full.pdf - Accepted Version
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277870_2_merged_1578581428.pdf - Submitted Version
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277870_2_supp_7956115_pvm1dt_convrt.pdf - Supplemental Material
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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: Article
Subjects: W General Medicine. Health Professions > W 20.5 Biomedical research
W General Medicine. Health Professions > W 20.55.V4 Veterinary biomedical research
WG Cardiovascular System > WG 20 Research (General)
WO Surgery > WO 20 Research (General)
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Digital Object Identifer (DOI): https://doi.org/10.1038/s41598-020-58650-y
Depositing User: Cathy Waldron
Date Deposited: 07 Feb 2020 15:17
Last Modified: 07 Feb 2020 15:17
URI: https://archive.lstmed.ac.uk/id/eprint/13570

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