SBIR Phase I: Novel partial cellular reprogramming method for the production of ex vivo blood

This Small Business Innovation Research (SBIR) Phase I project will develop advanced methods to temporarily reprogram hematopoietic stem cells (HSCs) that will enable ex vivo production of blood in quantities suitable for transfusion. A transfection-free method will be used that can be easily translated into clinical use. Every two seconds someone in the U.S. needs blood and more than 38,000 blood donations are needed every day. In order for ex vivo blood production to be clinically relevant, the expansion cell culture must be able to produce red blood cells in the range contained in a unit of blood: 2.5x1012cells. There exists a fundamental obstacle in reaching this number of cells. CD34+(HSCs) and erythroid progenitors are typically only capable of short-term, or restricted ex vivo expansion. The main objective of this project is to reprogram CD34+(HSCs) such that cellular mechanisms are activated to force cellular proliferation. Despite research efforts from around the world, reaching clinical significant quantities of blood in culture has not been previously possible. The goal is to produce clinically relevant quantities of blood and create a shift in clinical practice paradigms for the treatment of the anemic patient as well as the blood banking industry. What are the broader impacts of the proposed activity? The broader impact/commercial potential of this project, if successful, will be to create a viable alternative to allogenic blood transfusion, and compete with traditional blood banking and the use of recombinant erythropoietin (EPO). We expect that successful development of this technique will have a high societal impact on safety and availability of blood for transfusions as well as a reduction in hemolytic transfusion reactions. Although the safety of transfusions has improved markedly there is still a non-zero probability of getting HIV (1:1.8 Million), or Hepatitis C (1:1 Million). This work is expected to significantly enhance the scientific and technological understanding of ex vivo production of blood and provide a pathway to translation into clinical medicine. This project will have a significant impact in the $20 billion global blood transfusion market, as well as the EPO market, which is valued at about $53 Billion.