Project description
Cryopreservation of hepatocyte monolayers for drug toxicity screening
The goal of the EU-funded FAST_TOX project is to change how liver cells are cryopreserved for the toxicological testing market. Current standard procedures use isolated hepatocyte (liver cells) in toxicity screening. However, these cells must be stored frozen in suspension, while testing is undertaken on cells grown and attached to scaffolds as monolayers. Current methods do not allow cryopreservation of cells as monolayers, and the additional effort involved in processing, plating and growing the cells creates a bottleneck. FAST_TOX will use innovative cryoprotective polymers which allow cryopreservation of hepatocytes directly on the tissue culture plastic, enabling cell banking in an assay-ready format. Researchers have already obtained strong preliminary data demonstrating this concept in several cell lines, filed patents and shown that the polymer materials can be scaled up.
Objective
This proof of concept grant will transform how liver cells are cryopreserved for the toxicological testing market, translating scientific findings emerging from an ERC starter grant from lab to real application.
During the drug discovery process, the leading cause of new candidate drug rejection is the discovery of an unfavourable toxicological profile. It is essential to discover these as early as possible in the process to minimize costs and ensure favourable candidates are taken forward and to reduce the need for animal experimentation. The current standard screening method is using isolated hepatocyte (liver cells) to screen for toxicity. There is a disconnect however, in that these cells must be stored frozen in suspension, but all testing is undertaken on the cells grown attached to scaffolds as monolayers. It is not currently possible to cryopreserve cells as monolayers, and hence there is significant (time and financial) effort involved in processing, plating and growing the cells, acting as a bottleneck.
This project will use unique cryoprotective polymers, developed in an ERC starter grant, to enable the cryopreservation of hepatocytes directly on the tissue culture plastic, enabling for the first time banking of the cells in an ‘assay-ready format’. We have established strong preliminary data demonstrating this concept in other cell lines, and have filed patents and shown the synthesis can be scaled up.
In this project we will obtained essential data sets to demonstrate industrially-relevant cryopreservation of hepatocytes, but also emerging 3-D hepatocyte models (spheroids) to de-risk industrial translation and trigger licensing or investment. This will include not just scientific data but a cost-benefit analysis showing the economic gains due to reduced personnel effort required. There will be significant economic, but also societal benefit in optimising toxicological screening to improve the drug discovery process.
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Programme(s)
Funding Scheme
ERC-POC - Proof of Concept GrantHost institution
CV4 8UW COVENTRY
United Kingdom