Velocity, Key to Tissue Biopreservation
According to Sachi Norman, M.D., CEO of Core Dynamics, the firm’s goal with the use of the Multi-Thermal Gradient (MTG)™ freezing technology is to bring the “science fiction” of cryopreservation into the clinical reality of regenerative medicine.
The precise temperature control needed to properly freeze and store tissue is extremely difficult. It often leads to a significant decrease in cellular viability in response to direct structural damage from random ice crystal formation, as well as indirect damage through changes in cellular signaling, osmotic stress, and chemical toxicity.
MTG takes a different approach to biopreservation with the use of directional freezing. By regulating the velocity of a sample over a steady temperature gradient, well-controlled linear—rather than random—ice crystals can form, which greatly reduces the amount of structural cellular damage in frozen tissue.
The use of toxic chemicals such as DMSO is also not necessary. In preliminary clinical trials, Core Dynamics successfully applied MTG to the clinical cryopreservation and transplantation of osteoarticular grafts into the knee, explained Dr. Norman. It also transplanted fully functional frozen/thawed ovaries, which successfully lead to embryo development in sheep.
With a subsequent sublimation step, Core Dynamics has shown that viable frozen cells can be lyophilized and stored at room temperature. Effective reconstitution of lyophilized cells, due to an upregulation of reactive oxygen species (ROS) and other cellular stress, according to Dr. Norman, is a limiting factor; however, by optimizing the reconstitution fluid with antioxidants and other additives, cord blood stem cells were successfully lyophilized and reconstituted. They exhibited the same biochemical characteristics and increased cell viability compared to normal frozen cord blood cells.
In collaboration with the U.S. Army, Core Dynamics is now working to lyophilize, store, and reconstitute red blood cells. Although not yet clinically viable with a blood cell viability of 70% post-reconstitution, with constant optimization, Core Dynamics is close to perfecting lyophilized blood, said Dr. Norman, which would be a major advantage for healthcare, particularly in regions of the world that cannot afford expensive storage refrigerators and freezers.