Cryopreservation (CP) is a critical component in enabling on-demand access to biological material (macromolecules, cells, and tissues), yet CP has evolved little over the last several decades. Today's CP processes often yield a suboptimal "product," which has slowed progression in areas such as cell therapy and stem cell research. Recent discoveries focusing on molecular control and buffering of cell stress responses to CP as well as the development of new devices that improve sample freezing and thawing are now providing a path to improve sample quality. Numerous reports now identify the problems associated with CP-induced delayed-onset cell death (CIDOCD), with a focus on the mitigation of cell stress responses through freeze media formulation to optimize survival during "cold chain" sample management. Importantly, these new approaches that manage cell stress response are now providing a basis for advancements in cell therapy development. Herein, we provide an overview of the molecular stress responses of cells to CP, including the impact of hypothermic and cell death continuums and the strategies for improving preservation outcome.
Keywords: apoptosis; cryopreservation; cryopreservation-induced cell death; molecular control; necroptosis; thawing.