53. Pre-conditioning, epigenetics and other strategies

Abstract

In recent years there has been an explosion in various emerging approaches to assess and manipulate genetic integrity of cells and tissues at the phenotypic, cytologic, biochemical, and molecular level. These approaches can now be exploited with respect to cryo-stability. A better understanding of the implications of epigenetics, combined with renewed interest in cell differentiation and de-differentiation has opened new philosophies of biological mechanisms that can be developed to the advantage of future cryobiologists as they become better understood. For instance, new understanding of induction of pluripotency in somatic cells (e.g. iPS cells) has led to a better understanding of some fundamental mechanisms of cellular repair and propagation. A deeper understanding of the epigenetic influences on cell phenotype also shows great promise to help yield improved cryopreservation outcomes of cells, tissues and organs. Cellular reprogramming through molecular or environmental cues may be able to modulate cell pathways, inducing a rejuvenated state capable of restoring primary energy metabolism while avoiding free radical production post thaw. Better understanding of how to manipulate these mechanisms could potentially allow and induction of cryotolerance in difficult to freeze models to avoid quiescence or apoptosis post thaw. By combining these tools with novel chemistry and physics systems can be developed which will allow for more stable preservation through “classic” cryopreservation (e.g. slow cooling approaches), vitrification and potentially lyophilization.