Cold chain storage and distribution of therapeutic mammalian cell cultures including stem cells using sol-gel technology

Transport of cell cultures represents a significant distribution problem both for laboratory supply companies and for emerging therapeutics companies in the area of cell therapies and regenerative medicine. None of the current distribution solutions is ideal, involving a combination of complex, specialised, logistics with high costs and/or limited delivery time windows. This project will be aimed at further development of our recently invented novel technology for maintaining mammalian cell cultures in a quiescent state through short term storage and transport. It will be focused on the evaluation of the applicability of this novel technology as an effective ambient and/or cold chain temperature solution to an existing distribution problem affecting a broad range of human/mammalian cell cultures used or intended for use in cell based therapies.

To understand whether or not and how hydrogels, e.g. calcium alginate and Carbopol could be exploited as a structurally stable and inert scaffold for cell storage and transport, the kinetics of the viability of a range of cells within gels produced using a range of gelling conditions is to be examined. Cell viability, using established cell types, is to be examined in relation to various gelling and storage conditions including temperature, pH, CO2 concentration and polymer type. This will give us critical information on optimal gel conditions to preserve cell viability. We will expand our pilot study, which investigated a limited range of primary and secondary corneal epithelial cell lines to include cells from the endoderm and mesoderm. Cell viability will be assessed by standard means including, cell dead/alive assays, stress levels (p38 MAPK) within the cells, levels of differentiation by quantification of gene and protein levels and morphology by light and electron microscopy. Hydrogel structures will be characterised by rheology and electron microscopy. Commercialisation plans include protection of intellectual property in collaboration with the University's Technology Transfer Office as well as renewed market engagement with previously short-listed companies (established during BBSRC pathfinder award). Finally we aim to establish a collaborative development with an industrial partner.

The conventional method for the storage and shipment of mammalian cell cultures is to use frozen (cryogenic) methods. There are a number of difficult steps in preparing cells for freezing and recovering viable cells from the frozen state, but otherwise cells can be stored for prolonged periods of time in this condition. Since the recovery of viable cells from cryogenic storage requires specialist knowledge and equipment it is perceived to be a bottle neck in the expansion of cell based therapies. A viable alternative to cryopreservation for the shipment of cell based therapeutics is timely. Cell based therapies are set to increase rapidly over the next 10 years but the logistics of this new clinical approach have not been considered. The cost of frozen distribution can, in some cases, significantly exceed the value of the culture being shipped but there are currently no practicable alternatives. The biotechnology industry is rapidly expanding and the emerging field of tissue engineering/regenerative medicine is projected to have a high commercial impact in the near future. Within this field the transport of cell cultures has been identified as a bottleneck in the necessary future distribution. Presently none of the current distribution solutions is ideal, involving a combination of complex, specialised logistics with high costs and/or limited delivery time windows and various other technical challenges. Following recent discussions with Sigma-Aldrich, HPA Cultures, TCS Cellworks, Plasticell, Angel Biotechnology, ReNeuron and TiGenix the long term commercial benefits of a sol-gel storage system, as a platform technology, are impressive. Within the health care sector there are significant long term benefits if a biomaterial which can deliver stem cells from the lab to the clinic can be manufactured. The consequences would be an improvement in patient care as the transplants could be offered at the exact time they are needed, an increase in availability (i.e. not limited to donor numbers) and a significant saving in the costs associated with tissue bank management. These benefits can be realised 5 years on from completion of the current project and would expected to be financed by the MRC or NHS. Our biomaterial has been identified as a potential battle dressing with obvious benefits to the MOD. An sol-gel biomaterial that can maintain therapeutically active cells in a range of temperatures could be of significant use. The therapeutic cells could aid blood clotting or repair superficiail wounds such as burns. Using funding from the Centre for Defence Enterprise the time scale for a prototype would be short, 1-2 years. Further meetings are planned with our established industrial contacts and Dept of Biomedical Sciences, Defence Science and Technology Laboratory, Porton Down (Dr Chris Green and Dr Leah Scott).