Ex vivo model for the study of epicardium-targeted therapies

Lead Research Organisation: University of Surrey
Department Name: Biochemistry & Physiology


The recovery capacity of the adult heart after injury is severely limited by the low number of regenerating cells within this tissue. The epicardium, the most external layer of the heart, contains cells able to home to the injured heart muscle and promote its recovery. The models available to the scientists to study this phenomenon and develop strategies aimed at facilitating and improving the reparative process are limited and mainly based on regulated procedures (surgeries) performed on animals. In this project we will develop a model based on leftover pig heart tissues to mimic in a dish the behaviour of the epicardium after stimulation.
Pig hearts will be reduced to thin slices including both the epicardium and underlying heart muscle; the slices will be subjected to treatments to simulate the aftermath of heart disease and stimulated with known therapeutic substances to assess the capacity of our system to reproduce what has been observed in the animal models.
Once our model is tested, it will be used to develop new therapies harnessing the reparative potential of the epicardium.

Technical Summary

The emerging role of the epicardium in heart regeneration points at a largely unexplored reparative potential, boosting the number of studies focusing on this tissue. This project aims at developing an ex vivo model to study the epicardial cell behaviour in order to understand the observed in vivo reparative effect and provide a platform to enable future screening of arrays of gene/drug therapy candidates ex vivo, replacing animals in this type of studies.
We will base our model on the ex vivo culture of porcine superficial cardiac slices, comprising the epicardial layer and the underlying myocardial tissue (Epicardial/Cardiac-Tissue Slices, EpCardio-TS). Cardiac slices mirror the complexity of the heart tissue while allowing the high throughput approach needed for gene/drug discovery. Selective gene transfer to the epicardial cells is obtained by localised delivery of plasmid DNA mediated by a nanomaterial tool, the nanoneedles. The process of nanoneedles-mediated gene transfer (nanoinjection) efficiently delivers DNA to the cytoplasm of epicardial cells. Nanoinjection of reporter genes will allow the visualisation the cells within the tissue upon culture and will establish a proof of concept for future gene therapy applications. Post-fixation treatments leading to high tissue transparency will enable enhanced imaging of the epicardial cells throughout the cardiac slices. All these methods have been developed and optimised by the applicants and the named collaborators and will constitute the basis for the current project. This enabling model will contribute to further our understanding of the contribution of the epicardium to cardiac repair and improve the outcomes of therapies targeted to this tissue, reducing the burden to animals. The use of porcine heart slices will determine reduction of the number of small animals involved these in preclinical studies by substantially replacing the in vivo whole heart approach.


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