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 Brewer, Professor James and Garside, Professor Paul and Osii, Rowland and Scales, Dr Hannah and Lawton, Dr Jennifer and Meehan, Dr Gavin 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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| 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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