Transfer of the epicardial-cardiac organotypic culture model to support the ex vivo screening of gene therapy candidates

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

Abstract

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. We developed an innovative model based on thin slices obtained from leftover pig heart tissues that mimics in a dish the behaviour of the epicardium. In this project, we will teach other laboratories working on the epicardium how to prepare and use our model in their own research.
The adoption of our model by our partners will provide an alternative strategy to test their innovative gene therapy ideas, reducing their use of regulated procedures (surgeries) performed on animals.
In addition, we will present our model to several other interested laboratories and industrial partners working on similar science projects in order to encourage further uptake and further reduction of animal use.

Technical Summary

The emerging role of the epicardium in the heart regeneration points at a largely unexplored reparative potential, boosting the number of studies focusing on this tissue and increasing the number of animals used for this research. Most studies are performed in simplistic single cell culture or small animal models, raising scientific and ethical issues.
In our NC3R Project Grant, we developed a protocol for the preparation and ex vivo culture of superficial cardiac slices, comprising of the epicardial layer and the underlying myocardial tissue (EpCardio-TS), from abattoir porcine hearts (10-20 slices/heart) without further burden to animal life. Thanks to their structural complexity, representative of the heart tissue, and the high number slices obtained from each heart, this model allows the high throughput approach and the batch consistency needed for gene/drug discovery. Using a nanomaterial tool (nanoneedles) and a decolouration protocol (CUBIC), epicardial cells in EpCardio-TS can be transfected and/or labelled locally and visualised through the thickness of the slice.
This project aims at deploying our EpCardio-TS to two end user labs: Prof Stevens' lab at Imperial College London (primary end-user, London, UK) and Dr Martinez-Estrada's lab at University of Barcelona (secondary end-user, Barcelona, Spain).
Both end-user labs have ongoing projects aimed at the discovery of new genes influencing the epicardial reparative function and are planning to test the candidate genes in animal models of myocardial infarction. The introduction of EpCardio-TS to these labs will replace partially their reliance on small animals to screen their gene therapy candidates by an estimated 20%. The testimony and publications arising from the work of these outstanding collaborators, together with our planned local and international presentations, will further support the visibility and dissemination of EpCardio-TS.

Publications

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