Induction of Apoptosis in Response to Anhydrobiotic Conditions in Mammalian Cells

Abstract

Within many biomedical engineering subspecialties, there is a need for the reversible developmental arrest of cells and tissues in support of global distribution followed by on-demand restoration of cellular function (biopreservation). Recently, the field of anhydrobiotic (dry-state) preservation has emerged as a potential approach to achieve this goal. To date, investigations have focused on different approaches utilizing stabilizing molecules, such as trehalose, to achieve anhydrobiotic preservation, yet there remains a void in the understanding of the molecular-based physiological and biochemical responses of biologics to the desiccation process. Accordingly, we formulated and tested the hypothesis that apoptosis contributes to cell death following anhydrobiotic preservation through the activation of multiple pathways by the complex array of stressors associated with the desiccation process. In addition, we investigated the modulation of cell death following desiccation, hypothesizing that through inhibition of proteolytic caspase activation during the desiccation process, cellular tolerance would be enhanced. Data presented herein demonstrate that: (1) there is an activation of the apoptotic caspase cascade following desiccation, (2) as the extent of cellular desiccation increases so too does the level of apoptotic involvement, and (3) the inhibition of caspases during the process can improve cellular tolerance. Taken together, these data provide early evidence to suggest that the potential for targeted molecular modulation during the anhydrobiotic process may facilitate the successful anhydrobiotic preservation of biological material and its application into biotechnological settings.