Forsøksdyr: Revealing the ultra-structure and function of liver sinusoidal endothelial cells.

Godkjenningsdato 21.09.2020

Godkjenningsperiode 21.09.2020-20.09.2024

1 Purpose
The liver comprises of different cell types with different functions. The cells forming the walls of the small blood vessels of this organ, liver sinusoidal endothelial cells (LSEC), are a special type different to other vessel endothelial cells. They clear the blood of waste molecules and other harmful substances by allowing their transport from the blood to other liver cells through pores called fenestrations. We wish to study these cells and their pores as they age and after in vitro challenge with damaged fats and proteins. We must use fresh LSEC in these trials because this cell type changes quickly when removed from the body and the cells lose their fenestrations within 24 hours. We therefore need to isolate LSEC (50-100 million per liver) from rat livers. Using rats means that we need fewer animals for experiments, and we plan to make the most possible number of investigations with cells from each animal.

2 Distress
Very minor - the experiment on the rats will be terminal, and the only effect on the animal will be the induction of deep surgical anaesthesia prior to liver removal and euthanasia.

3 Expected benefit
Society and the hepatology field will benefit from greater knowledge about liver physiology, and better understanding as to why we lose liver sinusoidal endothelial cell fenestrations and other functions in disease and as we age.

4 Number of animals, and what kind
We plan to use 189 rats.

5 How to adhere to 3R
We plan to use 189 rats - we have arrived at this number by practising the 3Rs - carefully designing and refining experiments to reduce animal numbers and performing internet searches to avoid repetition of experiments/find replacements (there are none).