Descrizione del progetto
Crioconservazione di monostrati di epatociti per screening della tossicità farmacologica
L’obiettivo del progetto FAST_TOX, finanziato dall’UE, è modificare il modo in cui le cellule epatiche vengono crioconservate per il mercato degli esami tossicologici. Le attuali procedure standard utilizzano epatociti isolati (cellule epatiche) nello screening tossicologico. Tuttavia, queste cellule devono essere conservate congelate in sospensione, mentre gli esami vengono effettuati su cellule cresciute e attaccate a substrati come monostrati. I metodi attuali non consentono la crioconservazione di cellule come monostrati, e l’ulteriore sforzo implicato nell’elaborazione, nell’impianto e nella crescita delle cellule crea una strozzatura. FAST_TOX userà innovativi polimeri crioprotettori che consentono la crioconservazione di epatociti direttamente sulla plastica per coltura tessutale, favorendo il deposito delle cellule in un formato pronto per il test. I ricercatori hanno già ottenuto dati preliminari significativi che dimostrano questo concetto in molte linee cellulari, hanno depositato brevetti e dimostrato che i materiali polimerici possono essere estesi su scala industriale.
Obiettivo
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.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-POC - Proof of Concept GrantIstituzione ospitante
CV4 8UW COVENTRY
Regno Unito