Ex Vivo Bioengineering of Blood Products for Transfusion
Blood transfusions remain a life-saving treatment for millions worldwide. Major advances have been made in the development of alternative products for transfusions that bring us closer to having blood products that are pathogen-free, universally compatible, and can meet the demand. This session will present recent developments in manufacturing of bioengineered blood products focusing on development of novel blood substitutes as well as culture conditions to grow red blood and platelets from stem cells or immortalized cell lines.
Dr. Allan Doctor will discuss the challenges of successful oxygen carrier development. Classically, hemoglobin-based oxygen carriers (HBOCs) have failed in part due to ineffective oxygen release and over trapping of nitric oxide causing vasoconstriction. He will describe the design and features of bio-inspired design artificial red blood cells (ErythroMer), a novel HBOC which has overcome these weaknesses by controlling oxygen capture, release and attenuating nitric oxide uptake. Dr. Doctor will summarize pre-clinical results and discuss ongoing development, regulatory approaches, as well as potential novel indications enabled by this unique design.
Prof. Jan Frayne will discuss the development of progenitor cell lines for production of red blood cells. Various sources of stems cells from adult, cord blood, and induced pluripotent stem cells (iPSC) are currently used as ex vivo erythroid culture systems. As proof of principal of an alternative transfusion product, she will present data on the generation of immortalized erythroid lines which recapitulate adult erythropoiesis and provide a sustainable supply of red cells. Using a platform for CRISPR-Cas9 genome editing, sublines lacking one or more blood groups have also been created, thus generating more "universal' blood products and diagnostic tools. Data supporting additional applications will be presented. This will include highlighting the creation of cytokine independent lines for increasing the economic viability of ex vivo systems, lines as model cellular disease systems that can be used as research tools and drug screening platforms, and the use of lines for studying mechanisms of malaria parasite invasion.
Dr. Koji Eto will discuss the manufacturing of platelet like particle products from iPSC. Challenges remain in ex vivo manufacturing of the equivalent of one transfusion unit or roughly 200-300 billion functional platelets. He will describe the development of a megakaryocyte cell line as a master/working cell bank and present data demonstrating the production of clinical grade platelets. He will also discuss the use of a novel bioreactor, which applies turbulent energy with sheer stress to induce platelet biogenesis, and a process that incorporates steps in washing and concentrating the platelet preparations. Clinical applications of this design including the strategy of producing universal platelet products lacking human leukocyte antigens as well as next steps in industrial scale manufacturing will be discussed.
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