Ex-Vivo Perfusion of Human Hepatic Segments for the Ethical and Translational Study of Host Response to Infection

Ex-vivo perfusion technology is a revolutionary platform allowing for the development of human organ models which represent more ethical and translational alternatives to animal experimentation. This thesis presents a pioneering advance in the field of ex-vivo perfusion models, specifically focusing on the development of a human liver segmental ex-vivo perfusion model. This model not only represents a significant achievement in terms of technical innovation but also holds immense potential for conducting ethical and translational research on host response to infection. By employing this novel model, the intricate dynamics of the host-pathogen interaction can be explored in a controlled experimental setting, providing valuable insights into the underlying mechanisms, and facilitating the development of targeted interventions for infectious diseases. Following cannulation of the segmental hepatic artery and portal vein, nine human liver segments were perfused with two different oxygen carriers to develop and optimise the experimental model. Following this, six human liver segments underwent ex-vivo normothermic perfusion for six hours and were infected with three different mixes of Streptococcus pneumoniae serotypes. Regular perfusate and biopsy samples were taken for bacterial enumeration of each serotype. Non-cirrhotic human liver segments exhibited normal histology following six hours of ex-vivo perfusion with OxyglobinTM and formed the control group. Human liver segments failed to demonstrate bacterial elimination over the course of infection and the human liver did not differentiate between high and low virulence serotypes, contrary to revious observations reported in mice. This is the first research application of the human liver segmental perfusion model and cannot support results and conclusions previously observed in a murine model. This thesis highlights the importance of using ex-vivo human organ perfusion models to study host response to invasive disease as a more translational alternative to animal experimentation.