"A Tardigrade-Derived CAHS-Motif Enables Glycerol-Free Red Blood Cell Cryopreservation with Enhanced Low-Temperature Trehalose Loading and Synergistic Suppression of Ice Damage" ACS Applied Materials & Interfaces
Tardigrades, also called water bears, are famous for their ability to survive nearly anything. They protect themselves in extreme environments using proteins that researchers have developed into an efficient and effective strategy to preserve human red blood cells. Publishing in ACS Applied Materials & Interfaces, the researchers report that the technique, which is simpler than the current freezing method involving glycerol, restored red blood cell counts in anemic mice.
This study was our first attempt to translate a lesson from an extraordinarily resilient organism into a practical cell-preservation strategy." - Leming Sun
Tardigrades survive conditions that would destroy most other living things: freezing, dehydration, and the vacuum of space. Researchers even put tiny tattoos on them , and the animals don't seem to mind. By learning how these critters carry on, researchers hope to find ways to protect human cells.
One potential application is red blood cell cryopreservation - a process that stores rare blood types for long periods until they are needed. Blood cells are typically treated with glycerol to stop ice crystal formation during freezing. But glycerol must be removed before a transfusion, which causes cell damage. The tardigrade offers a simpler option: they have a protein called CAHS (cytosolic abundant heat-soluble), that it uses to keep itself going in extreme conditions. These proteins uniquely interact with trehalose, a sugar that stabilizes cell membranes and proteins. It's often used to reduce freezer burn in frozen foods. So, Hui Yang, Leming Sun, and colleagues wanted to explore whether combining CAHS proteins and trehalose could protect red blood cells in mice better than glycerol could alone.
"This study was our first attempt to translate a lesson from an extraordinarily resilient organism into a practical cell-preservation strategy," explains Sun, one of the corresponding authors of the study. "If further developed, it could make the process simpler after thawing, reduce concerns associated with residual glycerol, and help preserve the quality of stored cells."
Rather than using the full-length CAHS protein, the researchers determined that a section provided the desired protective effect. When combined with trehalose at a low temperature and then frozen in liquid nitrogen, the two components changed the way ice formed and melted, shielding cells from damage. And after thawing the cells, the CAHS-trehalose can easily be washed away by centrifugation. Up to 89% of the mouse red blood cells preserved with the new method recovered fully, compared to about 82% of the cells frozen using glycerol. Finally, the team tested the new cryopreservation approach and found that the blood cells were biocompatible after being frozen, thawed, and washed. In anemic mice, a transfusion with cryopreserved blood significantly improved their blood cell counts and hemoglobin levels without causing an inflammatory response.
The researchers hope that this work can help design better strategies for cryopreservation and even lead to protective strategies for blood that can function at room temperature.
The authors acknowledge funding from the National Natural Science Foundation of China, the Guangdong Basic and Applied Basic Research Foundation, and the Natural Science Basic Research Plan in Shaanxi Province of China.
