PROJECT SUMMARY
According to the most recent National Blood Collection and Utilization Survey (NBCUS), nearly
28,000 units (280 mL) of red blood cells (RBCs) are administered daily to transfusion recipients
in the United States alone. On an annual basis, over 10 million units are provided to people in
need of circulating RBCs. While the NBCUS concluded that healthcare providers were very
efficient in their use of stored units of RBCs, there are still complications that exist following
transfusion. Furthermore, local shortages of blood products available to healthcare providers
sometimes occur. In this proposal, the investigative team proposes a relatively simple modification
to the solution in which the RBCs are stored that will overcome the aforementioned shortcomings.
Specifically, the current FDA-approved storage solutions all have glucose concentrations
between 45-111 mM; the average healthy human has blood glucose levels of 4-6 mM and we
believe these hyperglycemic conditions are damaging the RBC in storage. Therefore, we
hypothesize that storing the cells in normoglycemic conditions (4-6 mM) and maintaining that
concentration with periodic feeding using a manual, proof-of-concept IV piggyback (IVPB), a
technique already used to drip reagents into a saline bag in hospitals, will lead to an improved
blood storage product. We will also test a novel rejuvenating solution based on C-peptide, the
31-amino acid peptide secreted from the pancreas in a 1:1 ratio with insulin. Preliminary data
shows our C-peptide-based rejuvenating additive can maintain important cell membrane and
metabolic properties for weeks into storage. We will test our solutions in a polyjet-printed
microfluidic device that mimics transfusion on a chip, while simultaneously monitoring key
secretion molecules that are determinants of blood flow and adhesion in vivo. Informed by our
early aims, we will test our normoglycemic storage solutions and rejuvenating strategy using
fluorescence-labeled RBCs in a mouse model of transfusion and radiolabeled RBCs in a larger,
sheep model of transfusion. Outcomes from these studies will be (1) an improved stored RBC
product that results in less post-transfusion complications for the recipient and (2) a product that
can be stored at least 2 weeks longer (56 days) than the current storage expiration time of 42
days. This extension of shelf-life would result in approximately 12,000 more units of available
stored blood over a 14 day period. Importantly, our method will not disrupt any aspect of current
blood collection and processing strategies, only requiring subsequent approval of less glucose in
the original collection and storage solutions, thus not disrupting current supply chain strategies.
