Goal 2: Reduce Human Disease

The potency and safety of transfusable red blood cells

Can we identify approaches to improve potency and/or safety of transfusable RBCs?


42 day pre-transfusion storage of RBCs maximizes utilization, while minimizing waste. However, RBCs undergo changes during collection, manipulation and storage that may reduce their potency or safety. Progress in understanding markers that predict transfusion success at the time of collection and with storage remains slow. New technologies have been proposed that may mitigate the storage lesion through new ways to process/prepare RBCs for transfusion.

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Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? : Compelling Question (CQ)

Details on the impact of addressing this CQ or CC :

While novel RBC storage methods have been described, the mechanisms underlying their efficacy has not been defined, a step that will be important for further improvements in this area. Some of these methods appear to improve efficacy of the RBC bioenergetic pathways; however, to date there have not been notable advances in reducing cytoskeletal defects common in stored RBCs. The development of new RBC preservation methods that minimize the impact of the storage lesion on specific areas of concern (e.g., diminished oxidation/peroxidation, decreased membrane fragility) is needed.


Use of ex vivo generated RBCs is an alternative to conventional donor-derived RBCs which can potentially improve product consistency, reduce the storage lesion, and improve safety. However, advances are needed before this approach is feasible on a large scale. While the development of blood substitutes including blood pharming will likely require more than 3-10 years before it can be ready for the clinic, Blood Pharming from hematopoietic stem/progenitor cells is now technically feasible and the recent development of genome editing methods suggests the exciting possibility of generating GMP compliant “immortal” stem cell sources to produce transfusable RBCs.

Feasibility and challenges of addressing this CQ or CC :

Research should include both pre-clinical and clinical studies to define optimal combinations of known factors preserving red cells (e.g. hypo-osmolarity, energy sources, antioxidants), and the development of methods for RBC pathogen reduction that do not increase the storage lesion.


Procedures for generating blood cells from cultured stem/progenitor cells is not currently cost-effective, limiting near term applications to special patient populations such as specific RBC phenotyping of rare donors for chronically transfused patients. Areas of research needed to advance the development of blood substitutes and blood pharming include: (a) new approaches to blood substitutes including artificial oxygen carriers generated from red cell lysates/components or engineered from combinatorial chemico-biological approaches (e.g., derivatization of hemoglobin, encapsidation of modulated oxygen carriers); (b) a better understanding of the biological properties of cultured RBCs with the goal of reducing blood pharming costs; (c) optimizing methods to expand stem cell populations while allowing differentiation to selected clinically relevant blood cell populations at clinically relevant levels; and (d) optimizing methodologies that faithfully replicate embryonic development to develop the cells of interest.

Name of idea submitter and other team members who worked on this idea : Nareg Roubinian, MD and Naomi Luban, MD for the NHLBI State of the Science in Transfusion Medicine


14 net votes
31 up votes
17 down votes
Idea No. 484