Exploring the application and mechanism of sodium hyaluronate in cryopreservation of red blood cells

The cryopreservation of red blood cells (RBCs) is essential for transfusion therapy and maintaining the inventory of RBCs units. The existing cryoprotectants (CPAs) have many defects, and the search for novel CPAs is becoming a research hotspot. Sodium hyaluronate (SH) is polymerized from sodium glucuronate and N-acetylglucosamine, which has good water binding capacity and biocompatibility. Herein, we reported for the first time that under the action of medium molecular weight sodium hyaluronate (MSH), the thawed RBCs recovery increased from 33.1 ​± ​5.8% to 63.2 ​± ​3.5%. In addition, RBCs functions and properties were maintained normally, and the residual MSH could be removed by direct washing. When MSH was used with a very low concentration (5% v/v) of glycerol (Gly), the thawed RBCs recovery could be increased to 92.3 ​± ​4.6%. In general, 40% v/v Gly was required to achieve similar efficiency. A mathematical model was used to compare the performance of MSH, PVA and trehalose in cryopreservation, and MSH showed the best efficiency. It was found that MSH could periodically regulate the content of intracellular water through the “reservoir effect” to reduce the damages during freezing and thawing. Moreover, MSH could inhibit ice recrystallization when combined with RBCs. The high viscosity and strong water binding capacity of MSH was also conducive to reducing the content of ice. This works points out a new direction for cryopreservation of RBCs and may promote transfusion therapy in clinic.