Chung, WY;
Wanford, JJ;
Kumar, R;
Isherwood, JD;
Haigh, RD;
Oggioni, MR;
Dennison, AR;
(2018)
An ex vivo porcine spleen perfusion as a model of bacterial sepsis.
ALTEX : Alternatives to Animal Experimentation
, 36
(1)
pp. 29-38.
10.14573/altex.1805131.
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Abstract
An ex vivo, porcine spleen perfusion model was established to study the early events occurring in the spleen prior to the onset of bacterial sepsis, using organs retrieved from animals slaughtered for food production. Porcine spleens were harvested from adult pigs and connected to a normothermic extracorporeal perfusion circuit. A constant perfusion of heparinized blood was performed for 6 hours. After injection of Streptococcus pneumoniae to the circuit serial samples of both blood and spleen biopsies were collected and analysed. Functionality of the perfused organs was assessed by monitoring the blood-gas parameters, flow rate and filtering capability of the organ. Interestingly, we observed full clearance of bacteria from the blood and an increase in bacterial counts in the spleen. Classical histology and immunohistochemistry on biopsies also confirmed no major damages in the organ architecture and changes in the immune cell distribution, other than the presence of clusters of pneumococci. A time-course study confirmed that each focus of infection derived from the replication of single pneumococcal cells within splenic macrophages. The model proposed – in line with the 3Rs principles – has utility in the replacement of experimental animals in infection research. Murine models are prevalently used to study pneumococcal infections, but are often not predictive for humans due to substantial differences in the immune systems of the two species. This model is designed to overcome these limitations, since porcine immunology and splenic architecture in particular, closely resemble those of humans.
| Type: | Article |
|---|---|
| Title: | An ex vivo porcine spleen perfusion as a model of bacterial sepsis |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.14573/altex.1805131 |
| Publisher version: | https://doi.org/10.14573/altex.1805131 |
| Language: | English |
| Additional information: | Articles are distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is appropriately cited (CC-BY). Copyright on any article in ALTEX is retained by the author(s). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10053797 |
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