Periodic Reporting for period 1 - FAST_TOX (BANKED HEPATOCYTE MONOLAYERS FOR ACCELERATING DRUG TOXICITY SCREENING)
Reporting period: 2020-09-01 to 2023-02-28
The aim of this PoC grant was to develop macromolecular cryoprotectant technology to allow the routine banking of cells in 2/3D format, so that they can be used off-the-shelf for toxicity testing. Toxicity testing of new drugs is a bottleneck in medicine discovery, and technologies which identify toxic compounds early are essential. Cryopreserved cells ‘ready to use’, could dramatically reduce the work-load and time for undertaking toxicity testing from up to 2 weeks to as little as 24 hours. The reason this has not been achieved previously, necessitating expensive and time consuming continuous culture, is because DMSO-cryopreservation (the gold standard) fails to protect cells when in monolayers (2D) or spheroids (3D). Hence, currently cells must be stored in suspension, and require significant effort to plate, grow and prepare them for testing. We aim to make cells ‘assay ready’ direct from the freezer. This project has successfully solved these problems and shown how cells can be stored as monolayers and contributed to the formation of a spin-out company.
Our core technology is based upon macromolecular cryoprotectants – polymers which can mitigate cold stress, using mechanism of action that standard, organic solvent, based cryoprotectants cannot. Firstly we demonstrated that cell monolayers of 3 different cell types can be cryopreserved as 2D monolayers leading to post-thaw recovery of the cells, with up to 2 fold increase compared to current technologies. This has also been extended to primary hepatocytes, which are in large demand for toxicity testing but do not always recover well post-thaw. Finally a challenging 3D spheroid model was cryopreserved, showing high recovery. For all cells (2 and 3D) model toxicological challenges confirmed they are suitable for drug screening. The results of this are now being commercialised in partnership with Cryologyx Ltd.
Our core technology is based upon macromolecular cryoprotectants – polymers which can mitigate cold stress, using mechanism of action that standard, organic solvent, based cryoprotectants cannot. Firstly we demonstrated that cell monolayers of 3 different cell types can be cryopreserved as 2D monolayers leading to post-thaw recovery of the cells, with up to 2 fold increase compared to current technologies. This has also been extended to primary hepatocytes, which are in large demand for toxicity testing but do not always recover well post-thaw. Finally a challenging 3D spheroid model was cryopreserved, showing high recovery. For all cells (2 and 3D) model toxicological challenges confirmed they are suitable for drug screening. The results of this are now being commercialised in partnership with Cryologyx Ltd.