Cryopreservation: Evolution of Molecular Based Strategies

Cryopreservation (CP) is an enabling process providing for on-demand access to biological material (cells and tissues) which serve as a starting, intermediate or even final product. While a critical tool, CP protocols, approaches and technologies have evolved little over the last several decades. A lack of conversion of discoveries from the CP sciences into mainstream utilization has resulted in a bottleneck in technological progression in areas such as stem cell research and cell therapy. While the adoption has been slow, discoveries including molecular control and buffering of cell stress response to CP as well as the development of new devices for improved sample freezing and thawing are providing for improved CP from both the processing and sample quality perspectives. Numerous studies have described the impact, mechanisms and points of control of cryopreservation-induced delayed-onset cell death (CIDOCD). In an effort to limit CIDOCD, efforts have focused on CP agent and freeze media formulation to provide a solution path and have yielded improvements in survival over traditional approaches. Importantly, each of these areas, new technologies and cell stress modulation, both individually and in combination, are now providing a new foundation to accelerate new research, technology and product development for which CP serves as an integral component. This chapter provides an overview of the molecular stress responses of cells to cryopreservation, the impact of the hypothermic and cell death continuums and the targeted modulation of common and/or cell specific responses to CP in providing a path to improving cell quality.