Cryoprotection of Platelets by Grafted Polymers

Abstract

Unlike red blood cells (RBC) which are stored at 4°C, platelets are stored at 22-24°C (room temperature) due to biophysical and biochemical changes induced by cold temperatures aggregately known as the 'cold storage lesion' (CSL). However, 22°C storage greatly increases the risk of microbial growth, thus limiting the safe storage of platelets to only 5-7 days (versus 42 days for RBC). Consequent to the short shelf life of platelets, blood services face chronic shortages of these life-saving cells. To overcome both the risk of microbial contamination and the constrained supplies of platelets, renewed research into attenuating the CSL and/or determining where cold stored platelets are clinically suitable are ongoing. In this chapter, we show that the covalent grafting of methoxypolyethylene glycol (mPEG), a biocompatible polymer, to the membrane of platelets attenuates the CSL. Moreover, the grafted mPEG serves as a potent cryoprotectant allowing platelets to be stored at 4°C, or frozen at −20°C, while retaining normal platelet counts and biologic function. The successful development of platelet PEGylation may provide a means by which the cold storage of platelets can be achieved with a minimal loss of platelet quality while improving both platelet microbial safety and inventory.

Effects and treatment applications of polymeric nanoparticles on improving platelets' storage time: a review of the literature from 2010 to 2020

“…According to previous studies, PEGylation can reduce the storage temperature of platelets to 4°C and even sub-zero temperatures without inducing any changes in platelet structure and viability. In addition, PEGylated platelets have also been used to prevent bacteria from reacting with platelets in platelet bags and to increase transfusion safety [ 72 ].…”

“…In this context, a methoxy-PEGylation (mPEG) approach was applied by Scott et al . [ 72 ] to reduce the temperature storage and PSL in mPEGylated platelets in an in vitro study. They showed that PEGylation of platelet membranes could reduce the PSLs in platelets.…”

“…This bond prevents the platelet surface glycoproteins from changing their shape and sticking together during storage. In addition, they showed that among PEGs, the optimum molecular weight for platelet PEGylation was between 2–5 kDa [ 72 ].…”

“…Therefore, it seems that surface modification of nanoparticles with nanoPEGylation can significantly increase platelet survival by inhibiting NP-induced platelet aggregation in platelet products [ 50 , 77 - 82 ]. In addition, PEGylation of platelets can improve platelet quality during storage [ 72 - 74 ]. As mentioned earlier, cooling platelets during storage time induces PSLs in them, which results in altered morphology, aggregation, granule release, survival, and the expression of surface markers in cold-stored platelets, while storage of platelets at 22–24°C protects platelets from these lesions [ 72 ].…”

“…In addition, PEGylation of platelets can improve platelet quality during storage [ 72 - 74 ]. As mentioned earlier, cooling platelets during storage time induces PSLs in them, which results in altered morphology, aggregation, granule release, survival, and the expression of surface markers in cold-stored platelets, while storage of platelets at 22–24°C protects platelets from these lesions [ 72 ]. However, this temperature increases the possibility of bacterial growth in platelet products, which reduces the safety of blood transfusions [ 72 , 74 , 75 ].…”