48. Understanding the molecular-based cell death continuum impact on biopreservation outcome

Abstract

The discipline of hypothermic medicine (Cryo) covers a wide diversity of applications ranging from organ transplantation to biopreservation of cells and tissues to cryoablation. With established techniques Cryo is often viewed as an “old school” discipline; yet, modern Cryo is in the mist of another developmental scientific and technological growth phase. In this regard, today’s Cryo finds itself at the forefront of research in the areas of molecular biology and bioengineering. 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 outcomes desired may vary significantly (preservation vs. ablation), the overall response profiles of biologics to low temperature exposure share a number of commonalities, as well as differences, at the molecular level. Recent studies have shown that the control and direction of these molecular responses significantly impacts final outcome. This presentation will provide an overview of 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. Further, discussion of the importance of targeted modulation of common and/or cell specific responses to cold and freezing temperatures in improving post storage cell, tissue and organ function will be discussed. This line of investigation has provided a molecular-based foundation guiding future research, technology development and cold chain processing.