Development of a GMP cryogenic cold chain for clinical delivery of Regenerative Medicine therapeutics
Lead Research Organisation:
University College London
Department Name: Medicine
Abstract
Treatment of liver diseases using a novel bioartificial liver machine (BAL) requires large numbers of liver cells, in a living state, to detoxify the patients' blood and support their body functions. It uses a circuit similar to that used for kidney dialysis. Liver cells have to be especially conditioned to carry out these tasks, which takes several days to achieve. As serious liver failure can develop rapidly, and often without warning, the bioartificial liver machine must be ready for "off the shelf" delivery to the clinic. This can only be achieved by frozen storage of the liver cells in sufficient numbers at very cold
temperatures (eg minus 150C).
The aim of our present work is to develop a new machine which can freeze large volumes and numbers of cells (eg about 1.5 litre) in a controlled fashion, so they can survive these very cold temperatures. Another important point is that the new cooling machine can be powered directly from mains electricity and thus does not
depend on the use of cold liquid gases, mainly liquid nitrogen, which are no longer considered safe to use for these purposes. These liquid gases are not sterile and may cause significant infection in materials which contact the patient. Thus on two counts (successful cooling of sensitive liver cells and avoidance of infection) this new equipment will be a great improvement on the current technology, and make the UK a leader in this field of science.
temperatures (eg minus 150C).
The aim of our present work is to develop a new machine which can freeze large volumes and numbers of cells (eg about 1.5 litre) in a controlled fashion, so they can survive these very cold temperatures. Another important point is that the new cooling machine can be powered directly from mains electricity and thus does not
depend on the use of cold liquid gases, mainly liquid nitrogen, which are no longer considered safe to use for these purposes. These liquid gases are not sterile and may cause significant infection in materials which contact the patient. Thus on two counts (successful cooling of sensitive liver cells and avoidance of infection) this new equipment will be a great improvement on the current technology, and make the UK a leader in this field of science.
Planned Impact
please see attached document as instructions are contradictory for this box and attachment requirements. We have added
Pathways to impact as an attachment.
Pathways to impact as an attachment.
Publications
Massie I
(2013)
Storage temperatures for cold-chain delivery in cell therapy: a study of alginate-encapsulated liver cell spheroids stored at -80°c or -170°c for up to 1 year.
in Tissue engineering. Part C, Methods
| Description | regenerative medicine therapeutics |
| Amount | £1,450,000 (GBP) |
| Organisation | Innovate UK |
| Sector | Public |
| Country | United Kingdom |
| Start | |
| Title | Adapted EF600 |
| Description | A controlled rate freezer has been adapated so that it can better simulate the cryopreservation process, in a way that has not been possible before. |
| Type Of Material | Model of mechanisms or symptoms - in vitro |
| Provided To Others? | No |
| Impact | It allows much more accurate in vitro simulations of the cryopreservation of large volumes in a cheaper and quicker manner. |
| Description | Industrial CASE collaborator |
| Organisation | Asymptote |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Asymptote have provided a controlled rate freezer. That freezer has been set up, optimised, and tested. The effects of some specific ice nucleating agents on hepatocytes has also been tested, which is of benefit to both parties. |
| Collaborator Contribution | Asymptote have provided a freezer for use in our lab. They have also adapted the freezer so it can be used for our experimental observations. Additionally they provided software that runs the freezer in a more advanced way. Additionally they have provided some modelling software that describes thermodynamic changes in a large volume in different conditions. |
| Impact | The collaboration is multi-disciplinary. The labs at UCL are primarily biological, doing medical research. Asymptote are mechanically building the freezer, requiring engineering, as well as some expertise in physics (primarilly thermodynanic modelling). The MRC CASE student working between both has a physics background, and needs to combine the biological needs of the cells to cryopreserve, with what can be enginnered physically. |
| Start Year | 2011 |