A42 Session 12: Cell Death Continuum: It’s Role in Cryomedicine: Molecular undercurrent of the cell death continuum in hypothermic medicine: Involvement in and impact on cryoablation and biopreservation outcomes alike

Abstract

The discipline of hypothermic medicine (Cryo) covers a wide diversity of application areas ranging from organ transplantation to biopreservation of cells and tissues to cryoablation. Often viewed as an “old school” discipline (established techniques historically yielding variable outcome), modern Cryo is in the mist of another growth phase from both the scientific and technology development perspectives. In this regard, today Cryo finds itself at the forefront of discovery in areas such as molecular biology and engineering. While covering a wide range of temperatures (∼4 °C to −196 °C, nominally) and exposure times (minutes to years), each Cryo application utilizes low temperature to depress or halt biological activity on a transient or permanent basis. While the ultimate outcome desired may vary significantly (preservation vs. ablation), the overall system response (cell, tissue, or organ) during and following exposure to low temperatures share a number of commonalities, as well as differences, at the molecular level. Ultimately it is the control and direction of these molecular responses which dictates final outcome (survival vs. destruction). This presentation will overview our current understanding of the molecular stress response of cells to low temperature exposure (ranging from ∼4 °C to −196 °C), the interrelated role of the apoptotic and necrotic cell death continuum and how this impacts outcome in a diversity of clinical and research settings including hypothermic storage, cryopreservation and cryoablation. Further, studies describing the impact of targeted modulation of common and/or cell specific responses to cold and freezing temperatures as a potential path to tailoring outcomes, from improved cell function to enhanced cancer ablation, will be discussed. These studies are now providing a molecular-based foundation and direction to stimulate new research, technology development and procedures as the use of and the knowledge base surrounding Cryo continues to expand, enabling continued improvements in overall efficacy and clinical outcomes.