Sub Normothermic Unfrozen Storage And Shipment Of Cells And Tissues For Therapy: Report From A Workshop Held At University College London May 2018

The difficulty in developing effective cryopreservation methods means that storage and shipment of cells in an unfrozen state at temperatures below typical culture conditions is often the means of cell supply considered by those shipping cells for therapy and diagnostic purposes. However, such storage could impact on the stability and suitability of cells for clinical use or diagnosis. A workshop of experts was organized (9th May at University College London) on the “sub normothermic unfrozen storage and shipment of cells and tissues”. A number of key regulatory issues were raised including lack of standardized analytical methodologies; the potential need for pre-use evaluation after the cell product had been released and shipped for use, and the significant challenge of introducing new storage and shipment conditions in the absence of historic validation data. Reduced temperature and oxygen tend to inhibit metabolic rate and were identified as key factors in enabling stability of viability and function during storage. However, it was concluded that there were a wide range of biological effects in the 0-4oC range even in simple cellular systems which include cold-shock protein induction, formation of membrane holes and waxy lipids in membranes. Even at higher temperatures changes such as surface molecule crosslinking could affect product quality. A number of commercial reagents and new hydrogels were identified which had been applied successfully to store certain cell types. However, storage solutions were often derived empirically and published data often used diverse viability assessment methods which made comparison of results with the different reagents very difficult. Key requirements identified for future research outputs were enhanced viability assays supported by a better understanding of fundamental biochemistry and investigation of small molecules which may have beneficial effects for cell shipment.