The ESR appointed to this project will learn how to induce acute kidney injury in mice, using a surgical approach of ischaemia reperfusion. This acute kidney injury model will then be employed to assess the safety and efficacy of mesenchymal stromal cells (MSCs) of different origins. We will also explore the therapeutic potential of MSC-derived extra-cellular vesicles (ECVs). This aspect will be performed in close collaboration with other RenalToolBox ESRs.

The safety assessment will involve imaging of whole body and organs to detect possible tumour formation using a range of preclinical imaging instruments at UoL’s Centre for Preclinical Imaging (CPI). Efficacy will be assessed using established biomarkers of renal injury and by monitoring renal function longitudinally. At the end-point of each study, various histological and immunohistochemical analyses will be undertaken to detect the administered cells and quantify the extent of histological damage.

Multivariate data modelling will be applied to characterise changes in renal function over time using multivariate mixed-effects models. The models will take into account the longitudinal nature of the data as well as the fact that the cells will come from different sources (ESR projects). The correlation structure of the dataset will be investigated and the various efficacy outcomes will be jointly analysed. The study will be carefully designed to minimise potential sources of bias.

The student will be trained in all aspects of animal handling, surgery and use of the imaging instruments (supervised by Dr Bettina Wilm). The student will also be trained to undertake histological analyses (supervised by Dr Lorenzo Ressel) and how to perform the appropriate statistical tests (Dr Marta Garcia-Finana).