Industrially generated red blood cells for transfusion

Blood Transfusion has become a mainstay of modern medical practice. However problems persist both nationally and internationally in maintaining supply, managing the risk of transmission of infectious agents and ensuring immune compatibility between donor and recipient. There is therefore a massive unmet and increasing clinical demand for blood. In the UK alone 2.2 million units of blood are used each year.

Human embryonic stem cells (hES cells) have unique properties in that they can be maintained indefinitely in culture in an undifferentiated state and yet retain the ability to form all the cells and tissues within the body. They offer a potentially limitless source from which to generate red blood cells (RBCs) for use in clinical transfusion. A collaborative research team from the University of Glasgow, Heriot-Watt University, the University of Edinburgh and the University of Dundee has been working on developing and scaling up a process to produce RBCs in suspension culture from hES cells. This will allow the on-demand production of universal donor blood with no risk of human virus transmission.

The work presented here will describe some of the biological and engineering challenges associated with scale-up of the cell culture and separation operations used to produce the large numbers of RBCs necessary for potential clinical supply. Regulatory and supply chain issues associated with a live cell product will also be discussed since regulatory bodies are almost certain to require as stringent a demonstration of purity as is currently demanded for protein therapeutics.

Although this presentation describes development of a specific process, it is likely that the greatest scale-up hurdles will be specific to cellular therapies as a whole; therefore it is timely to consider process development now in order to prevent a major bottleneck occurring when allogeneic cellular therapies reach clinical trials.