Optimal Rewarming Solutions for Cryopreserved Tissue Systems

CPSI Biotech personnel have developed solutions and devices for the cryopreservation and hypothermic storage of human cells and tissues. Devices being -tested include SmartFreeze and SmartThaw - instruments designed for the improved cryopreservation and thawing of stem cells to be used for stem cell therapy. This SBIR grant application proposes to identify pre-conditioning and post-conditioning agents that can be coupled to standard vitrification protocols such that improved post-thaw tissue viability and function are achieved. This new paradigm, PVP (Pre-conditioning, vitrification and post-conditioning), is built on CPSI's 20 year experience analyzing the cold-stress pathways activated in cryopreserved/hypothermically-stored human cells. The Tasks proposed involve testing cell stress modulators shown by CPSI to improve hypothermic storage by up to 90%, combining promising candidates into prototype pre-/post-conditioning cocktails, and focusing on the potential role of resveratrol/sirtuin genes in the PVP process. Phase 2 will be dedicated to optimizing the PVP protocol and developing a second generation PVP-compatible SmartThaw device for human tissue and organ warming. In summary, the hypothesis to be tested is that modulating the cell stress pathways that are triggered by vitrification will improve this cryopreservation process which, in turn, will make whole organ vitrification possible in the near term.