Investigation of optimal gel conditions for stem cell preservation at room temperature and scaling up of selected methodology

For numerous reasons (financial, resource, scientific etc) the centres of excellence responsible for the preparation/manufacture (cell banking, growth, culture, purity and QA etc) of the Living Biologic (LB) in any Regenerative Therapeutic (RT) are geographically separated to that of the point of use. Therefore, a major challenge is to deliver to the clinic the LB in a validated, quality, 'fit for purpose' form. Across the global market place there is a pressing need to retain the key LB characteristic for at least several days to one week. Although suitable for longer term banking, Cryofreezing for the final product is not an option due to the acknowledged negative effects on the LB. As important, the system needs to be simple, rapid and easy to use at the point of care in order to ease uptake by the clinician. Our recent BRIC enabling grant has shown that an alginate gel cell encapsulation system meets many of these needs. We have a growing body of evidence that demonstrates it is effective at preserving a number of cell types (including stem cells) over extended periods in room temperature conditions. However, further research is needed to fully understand how it works and demonstrate that the technology can be implemented in an industrial setting (i.e. scalable).

Successful outcome from this project will significantly advance regenerative medicine product development as it will solve the control of distribution/thawing/administration of these complex cellular medicines. Implementing such a step-change in the way cell therapies are distributed will open up novel opportunities and encourage big-pharma's interest in the sector (as a major bottleneck in the product value-chain is reduced).
There is currently an unmet need. Our solution - a simple hydrogel capable of encapsulating and holding stem cells in suspension for up to 1 week at room temperature and atmospheric carbon dioxide. Therefore no need for complicated freezing/thawing systems or the inconvenience of shipping at low temperatures.
With the assistance of chemical engineers we will explore the manufacturing process of hydrogels for stem cell encapsulation in biopolymers with controlled porosity and mechanical properties using an aqueous-in-oil emulsification approach (in which the Co-I is a leading expert). Parallel to this we will investigate the underlying mechanisms that allows for the excellent preservation of stem cells at room temperature once encapsulated within a biopolymer hydrogel. Building upon our exciting (BRIC enabling funded) proof-of-concept results, which have demonstrated the potential of this technology in the regenerative medicine field, we aim to explore its application in commercial settings with the collaboration of BRIC members.

The proposed programe of work fits within the BRIC Industry priority research area "Bioprocessing research for cellular products".
As the proposal will investigate the use of marine alage in the bioprocessing of cellular products is also closely aligned to the BBSRC Industrial Biotechnology and Bioenergy Highlight Notice 1. However we have not indicated this within the clasification of the proposal.

The market demand for an innovative solution to shipping cell therapeutic products is significant and is expected to grow annually in the mid-term. The recent UK Remedi grant reported that the cell therapy sector has increased significantly over the last five years - composed of 138 primary firms and 49 secondary firms.
Therefore the most immediate beneficiaries will be regenmed SMA's looking for a robust, low cost method to ship cells to academic collaborators, business to business (QA, regulatory bodies etc.) and health-care practitioners. This would be achieved within 2-3 years of the project starting.
The realisation of cell based therapies would move a significant step forward due to the ease and relative low cost to transport of the living biologic, reducing costs for health care providers, ultimately resulting in patient benefit through improved quality of life and health. This would be achieved within 4-8 years of the project starting.
The capability to move cells around without the need for cold storage would open up new areas for the application of cells. Such areas might be on the battle field. We estimate (using our current hydrogel formulations) that enough red blood cells for an emergency blood transfusion could be encapsulated within 330ml flask. If cryo-storage can be combined with ambient storage (to be explored within work package 3) personal blood transfusion kits could be stored cryogenically (eg Camp Bastion) then issued to troops to be kept with them for a week or more. Currently the rule of thumb is that for each 24 hours at room temperature (ie 25 *C) red blood cells lose about a week's worth of refrigerated storage. It may be possible to improve this dramatically.
Other beneficiaries may include companies of government bodies that use cell based assays. Currently this type of assay requires the use of standard aseptic technique (safety cabinet, clean equipment, specialised knowledge etc). However by encapsulating cells it is possible that certain assays could be completed in the field (as the cells remain aseptic within the gel). One example could be environmental toxicity testing using a specific cell viability as an end point which would be assessed colormetrically in the field.
Importantly the propsal will have significant impact upon our understanding of the bioprocessing of materials with cells pre-encapsulated. This area has previously been given little consideration.