Grant: Operating Grant

Cryobiology is the study of the effects of extremely low temperatures on biological systems. A major application is the low-temperature storage (cryopreservation) of cells and tissues for transplantation to treat injury and disease. While many cell types have been successfully cryopreserved and used clinically for decades, some cells and the vast majority of tissues encounter significant problems during cryopreservation. For example, a widely transplanted tissue is cornea, the clear tissue of the eye through which people see. The endothelial monolayer is a layer of cells on the inner surface of the cornea that is critical to the health of the cornea and understood to be a limitation for cryopreservation techniques. Individual corneal endothelial cells can be cryopreserved in suspension when isolated from the tissue. However, the endothelial monolayer of cells in the cornea cannot be adequately cryopreserved without considerable cell loss resulting in loss of cornea function. This prevents the routine transplantation of cryopreserved corneas. Similarly, amniotic membrane is a tissue discarded after childbirth. While amniotic membrane is currently cryopreserved and used in surgeries of the eye and skin, an understanding of the cryobiology of this tissue is required to effectively cryopreserve larger pieces of this tissue with increased cell viability for expanded clinical use. As cellular therapies and transplant of both natural and engineered tissue are increasingly used in modern medicine, there is an urgent need for effective cryopreservation strategies. The objective of this proposal is to combine advanced engineering modeling, cryobiological expertise, and biological experimentation to develop key understanding of identified issues in cell and tissue cryopreservation with immediate application to corneas and amniotic membrane. Proposed experiments will use cultured cells, animal tissue discarded during meat production, and human tissue discarded after childbirth.